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Objective A high NOBLADS score reflecting the severity of lower gastrointestinal bleeding contributes to the identification of stigmata of recent hemorrhage (SRH) in colonic diverticular bleeding (CDB). The burden of colonoscopy is particularly high in elderly patients; therefore, we investigated the utility of the NOBLADS score for managing CDB by age stratification. The NOBLADS score performance in SRH prediction was estimated by the area under the receiver operating characteristic calculation and a multiple logistic regression model. Methods This was a single-center, retrospective cohort study. Patients who underwent initial colonoscopy with CDB between April 2008 and December 2019 were divided into a young group (65 years old) and an elderly group (≥65 years old). We further categorized patients according to colonoscopy findings as SRH-positive, with successful endoscopic hemostasis performance, and SRH-negative, with suspected CDB. The main outcome measure was successful SRH identification. Results Four-hundred and seventeen CDB patients were included, of whom 250 (60.0%) were elderly. There were 72 (43.1%) SRH-positive patients in the young group and 94 (37.6%) in the elderly group. The areas under the receiver operating characteristic curves of the NOBLADS score predicting SRH identification were 0.76, 0.71, and 0.81 for all ages, young patients, and elderly patients, respectively. A multiple logistic regression analysis showed that SRH identification was significantly associated with NOBLADS scores in both groups. Eighty-one patients (32.4%) scored ≥4 in the elderly group, and 60 of those were SRH-positive (74.1%). All 27 patients (10.8%) who scored ≥4 with extravasation on computed tomography were found to have SRH. Conclusion The NOBLADS score is useful for predicting SRH identification, especially in elderly patients.

IntroductionBronchodilators, including long-acting muscarinic antagonists (LAMA) and long-acting beta 2 agonists (LABA), are the main treatments for chronic obstructive pulmonary disease (COPD). The efficacy of triple therapy (inhaled corticosteroids/LAMA/LABA) has also been reported. However, the effect of triple therapy on patients with mild-to-moderate COPD has not yet been clarified. This study aims to investigate the safety and efficacy of triple therapy, compared with LAMA/LABA combination therapy, for lung function and health-related quality of life in patients with mild-to-moderate COPD and identify baseline characteristics and biomarkers to predict responders and non-responders to triple therapy.Methods and analysisThis is a multicentre, prospective, open-label, randomised, parallel-group study. Mild-to-moderate patients with COPD will be randomised to receive fluticasone furoate/umeclidinium/vilanterol or umeclidinium/vilanterol for 24 weeks. A total of 668 patients will be enrolled from March 2022 to September 2023 from 38 sites in Japan. The primary endpoint is the change in the trough forced expiration volume in 1 s after 12 weeks of treatment. Secondary endpoints are responder rates based on the COPD assessment test score and the St. George’s Respiratory Questionnaire total score after 24 weeks of treatment. The safety endpoint is the occurrence of any adverse events. We will also investigate safety in terms of changes in microbial colonisation in sputum and antimycobacterium avium complex antibodies.Ethics and disseminationThe study protocol and informed consent documents were approved by the Saga University Clinical Research Review Board (approval number: CRB7180010). Written informed consent will be obtained from all patients. Recruitment of the patients began in March 2022. The results will be disseminated through scientific peer-reviewed publications and domestic and international medical conferences.Trial registration numbersUMIN000046812 and jRCTs031190008.

Introduction: Colonic diverticulosis increases with age, leading to a higher risk of colonic diverticular bleeding (CDB) in the elderly. As life expectancy continues to increase, the need for endoscopic hemostasis for CDB in the elderly can also be expected to increase. However, there have been no reports to date on the feasibility of endoscopic hemostasis for elderly CDB patients. Several recent studies have addressed the effectiveness of endoscopic band ligation (EBL) for CDB. In this study, we evaluate the safety and effectiveness of EBL in elderly CDB patients compared to younger CDB patients. Methods: We retrospectively analyzed the medical records of consecutive patients treated with EBL for the first time at a tertiary referral center between March 2011 and November 2017. Patients were grouped according to age into those at least 75 years old (the Elderly) and those Results: EBL was performed in 153 patients during the study period (49 Elderly patients and 104 Nonelderly patients). Elderly patients were less likely to be male (p < 0.001) and had lower hemoglobin levels on admission (p < 0.001). Bleeding on the right side of the splenic flexure was observed more frequently in the Nonelderly (p = 0.002). Charlson Comorbidity Index (CCI) and use of antithrombotic agents were significantly higher in the Elderly (p < 0.001 and p < 0.001, respectively). Active bleeding tended to be observed more frequently in the Elderly (p = 0.054), while the difference was not significant. There were no significant differences in the shock index, procedure time, or units of packed red blood cells transfused between the 2 groups. No significant differences in the technical success rate (97.1 vs. 98%, p = 0.76), early rebleeding rate (10.2 vs. 14.4%, p = 0.47), or other complications (2 vs. 1%, p = 0.58) were observed. Perforation and abscess formation were not observed in either group. Female gender, left-sidedness, higher CCI, and lower hemoglobin level were all significantly more frequently observed in the Elderly on multiple logistic regression analysis. Discussion/Conclusion: EBL may be similarly safe and effective for the treatment of CDB in the elderly as in the nonelderly.

Inhaled medication is the cornerstone of pharmacological treatment for asthma. Poor inhaler techniques are associated with poor asthma control and an increased risk of exacerbations. Leaflets and videos are provided by several pharmaceutical companies to explain the proper techniques to patients. We investigated the effects of instructional materials (leaflet and video) on the patient's inhaler techniques.The subjects were 67 medical students at Kagoshima University. They all were provided with two types of inhalation devices: a dry powder inhaler (DPI) and a pressurized metered-dose inhaler (pMDI). The students were assigned to three groups: (1) leaflet, (2) video, and (3) combination (leaflet + video). Pulmonologists observed and assessed the students' use of the devices by using a validated checklist. The percentage of subjects who avoided critical errors was also assessed. Critical errors were errors that affected drug delivery to the lungs substantially.The percentage of overall competence and the number of steps that were mastered out of the 11 steps were higher in the combination group than those in the other two groups. However, only 40% in the combination group were able to successfully execute every critical step. The percentage of subjects who avoided critical errors was also higher in the combination group than in the other groups.A single form of instructional materials (leaflet or video) was insufficient for acquiring proper inhaler techniques. The combination of two learning materials may help patients with asthma acquire proper inhaler techniques and subsequently, improve their asthma control.

Background and Aims The identification of stigmata of recent hemorrhage (SRH) in colonic diverticular bleeding (CDB) enables an endoscopic treatment and can improve the clinical outcome. However, SRH identification rate remains low. This study aims to investigate whether NOBLADS and Strate scoring systems are useful for predicting SRH identification rate of CDB pre‐procedurally via colonoscopy. Methods In this single‐center retrospective observational study, 302 patients who experienced their first episode of CDB from April 2008 to March 2018 were included. Patients were classified into SRH‐positive and SRH‐negative groups. The primary outcome was SRH identification rate. The secondary outcomes were active bleeding in SRH and early rebleeding rates. The usefulness of the NOBLADS and Strate scores as predicted values of SRH identification was evaluated using the area under the receiver operating characteristic curve. Results There were 126 and 176 patients in the SRH‐positive and SRH‐negative groups, respectively. The area under the receiver operating characteristic curve for SRH identification using the NOBLADS score was 0.74 (95% confidence interval, 0.69–0.80) and that using the Strate score was 0.74 (95% confidence interval, 0.68–0.79). Active bleeding and early rebleeding rates increased according to each score. By setting the cut‐off of the NOBLADS score to four points, treatment was possible in 70.2% (66/94) patients. Addition of extravasation at computed tomography to a NOBLADS score of ≧ 4 points allowed treatment of all patients (24/24). Conclusions Severity scoring in acute lower gastrointestinal bleeding was effective for predicting SRH identification in CDB. We suggest that combination of these scorings and CT findings could offer a new therapeutic strategy.

Asparagine-linked glycosylation (N-glycosylation) of proteins in the cancer secretome has been gaining increasing attention as a potential biomarker for cancer detection and diagnosis. Small extracellular vesicles (sEVs) constitute a large part of the cancer secretome, yet little is known about whether their N-glycosylation status reflects known cancer characteristics. Here, we investigated the N-glycosylation of sEVs released from small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC) cells. We found that the N-glycans of SCLC-sEVs were characterized by the presence of structural units also found in the brain N-glycome, while NSCLC-sEVs were dominated by typical lung-type N-glycans with NSCLC-associated core fucosylation. In addition, lectin-assisted N-glycoproteomics of SCLC-sEVs and NSCLC-sEVs revealed that integrin αV was commonly expressed in sEVs of both cancer cell types, while the epithelium-specific integrin α6β4 heterodimer was selectively expressed in NSCLC-sEVs. Importantly, N-glycomics of the immunopurified integrin α6 from NSCLC-sEVs identified NSCLC-type N-glycans on this integrin subunit. Thus, we conclude that protein N-glycosylation in lung cancer sEVs may potentially reflect the histology of lung cancers.

Amyloidosis is a syndrome involving amyloid protein deposition in various organs, resulting in organ dysfunction. Symptoms of gastrointestinal amyloidosis are usually nonspecific, such as diarrhea and body weight loss. We, here, report a patient who presented to the hospital with simultaneous hematemesis, melena, and intestinal pseudo-obstruction, leading to a diagnosis of primary gastrointestinal amyloidosis based on computed tomography (CT) and endoscopic findings. CT showed diffuse wall thickening from the duodenum to the jejunum, jejunal dilation, and fluid accumulation throughout the gastrointestinal tract. Upper gastrointestinal endoscopy revealed duodenal mucosal edema, jejunal dilation, and small hemorrhages from jejunal mucosal erosion. The definite diagnosis was done based on biopsy results. This report describes the early diagnosis of gastrointestinal amyloidosis based on CT and endoscopy findings.

Basaloid squamous cell carcinoma of the esophagus is rare and generally detected at advanced stage, and its prognosis is poorer than that of conventional esophageal squamous cell carcinoma. Therefore, detection at the early stage is crucial for patient survival. We experienced an elevated esophageal basaloid squamous cell carcinoma presenting as a subepithelial tumor-like lesion. Although the lesion needed to be differentiated from subepithelial tumor, we diagnosed it as early stage and treated with endoscopic submucosal dissection. We report the macroscopic and microscopic findings of basaloid carcinoma through this case along with a review of the relevant literature.

BACKGROUND Tiotropium bromide, a long-acting muscarinic antagonist, reduces the frequency of exacerbation in patients with moderate to severe asthma, but its underlying mechanism is not clear. Asthma exacerbations are associated with exposure to external stimuli, and group 2 innate lymphoid cells (ILC2s) are considered to be involved in the pathophysiology of asthma exacerbation. We investigated whether tiotropium modulates airway inflammation through ILC2 functions. METHODS Mice were administered papain intranasally to induce innate-type airway inflammation with or without tiotropium pretreatment, and bronchoalveolar lavage fluids (BALF) and lung tissues were collected. Lung-derived ILC2s and bone marrow-derived basophils were stimulated in vitro with IL-33 in the presence or absence of tiotropium. Muscarinic M3 receptor (M3R) expression on immune cells was assessed by RNA sequence. RESULTS Papain induced airway eosinophilic inflammation, and tiotropium reduced the numbers of eosinophils in BALF. The concentrations of IL-4, IL-5, and IL-13, and the numbers of ILC2s in BALF were also reduced by tiotropium treatment. However, tiotropium did not affect IL-33-induced IL-5 and IL-13 production from ILC2s, suggesting that tiotropium regulates ILC2s indirectly. Gene-expression analysis showed that basophils predominantly expressed M3R mRNA among murine immune cells. Tiotropium reduced IL-4 production from basophils derived from mouse bone marrow and human basophils after stimulation with IL-33. CONCLUSIONS These findings suggest that tiotropium attenuates ILC2-dependent airway inflammation by suppressing IL-4 production from basophils and, subsequently, regulating ILC2 activation. The inhibitory effects of long-acting muscarinic antagonists on the innate response may contribute to reducing asthma exacerbation.

Background and Aim Endoscopic band ligation (EBL), used for the treatment of colonic diverticular bleeding, has a lower rebleeding rate than endoscopic clipping. However, different devices are used in Japan and the Western countries; no animal studies have been conducted to elucidate the safety of such devices. We compared two EBL devices, the first used in Japan and the second used in Western countries. Methods and Results The Japanese and Western EBL devices were compared by assessing the EBL safety at 40 sites in an animal model with a normal colon that is anatomically similar to the human colon. Macroscopic and pathological examinations were performed to evaluate the layer ligated by the band and the presence of perforation. The findings on day 1 and day 7 after EBL were compared. The ligated layer was the muscularis propria at 39 sites; the layer was not evaluated at one site where the band was unintentionally removed during the endoscopic procedure. Pathologically, there was no perforation at any of the assessed sites. There was no statistical difference in any of the pathological variables between the two devices or between days 1 and 7 after EBL. The total procedure time was significantly shorter with the Western EBL device. Conclusions In this animal study, both evaluated devices were safe for EBL, without differences in the macroscopic and pathological variables after EBL. Ligation of the muscularis propria layer did not result in perforation., We performed endoscopic band ligation (EBL) on colons of pigs using two different EBL devices and compared the macroscopic and pathological findings to evaluate the efficacy and safety of the two EBL devices, the first used in Japan and the second used in Western countries. Our results indicated that both evaluated devices were safe for EBL. A suitable device can be selected according to the patients' clinical condition.

A 64-year-old Japanese man with no significant medical history presented with epigastric discomfort of 2-weeks’ duration. He was diagnosed with metastatic HER2-positive gastric cancer. Chemotherapy with capecitabine, oxaliplatin, and trastuzumab was initiated. During the eighth cycle, he suddenly complained of electric shock-like pain in both legs upon neck flexion, consistent with Lhermitte’s sign. Oxaliplatin was discontinued, and Lhermitte’s sign resolved after 3 months. Neurotoxicity is commonly observed in platinum-based chemotherapy, but Lhermitte’s sign is rare. This is the first report of oxaliplatin-induced Lhermitte’s sign in a gastric cancer patient.

Pulmonary arterial hypertension (PAH) has a major effect on life expectancy with functional degeneracy of the lungs and right heart. Interleukin-13 (IL-13), one of the type 2 cytokines mainly associated with allergic diseases, has recently been reported to be associated with Schistosomiasis-associated PAH which shares pathological features with other forms of PAH, such as idiopathic PAH and connective tissue disease-associated PAH. But a direct pathological role of IL-13 in the development of PAH has not been explored. We examined the effects of recombinant human IL-13 on the function of primary human pulmonary artery endothelial cells (HPAECs) to examine how IL-13 influences exacerbation of PAH. IL-13 increased the expression of Rictor, which is a key molecule of mammalian target of rapamycin complex 2. Treatment of IL-13 induced HPAEC migration via Rictor. Rictor was directly regulated by both miR-424 and 503 (miR-424/503). Therefore, IL-13 increases Rictor level by regulating miR-424/503, causing the increase of HPAEC migration. Since enhancement of HPAEC migration in the lung is thought to be associated with PAH, these data suggest that IL-13 takes some roles in exacerbating PAH.