Gastroduodenal Mucosal Injury in Patients Taking Low-Dose Aspirin and the Role of Gastric Mucoprotective Drugs: Possible Effect of Rebamipide

The present study was conducted to investigate the prevalence of mucosal injury in patients taking low-dose aspirin in Japan and examine the effect of gastric mucoprotective drugs on aspirin-related gastroduodenal toxicity. We selected 530 patients who had taken low-dose aspirin for 1 month or more after undergoing esophagogastroduodenoscopy from 2005 through 2006 at Teikyo University Hospital, Tokyo, Japan. Endoscopic records were retrospectively reviewed to determine the presence of massive bleeding and mucosal injury (ulcer or erosion). The influence of clinical factors, including co-administration of gastroprotective drugs, was also examined. Hemorrhage was observed in 25 patients (3.7%) and mucosal injury (36.2%) in 192 patients. The presence of Helicobacter pylori antibody was a significant risk factor associated with mucosal injury. Patients taking any gastroprotective drug showed a significantly lower rate of mucosal injury than those not taking these drugs. Patients taking rebamipide concomitantly with proton pump inhibitors or histamine 2 receptor antagonists had mucosal injury less frequently than those taking acid suppressants plus other mucoprotective drugs. In conclusion, these results show the possible gastroprotective effects of rebamipide, suggesting that it may be a good choice in aspirin users with gastroduodenal toxicity that is not suppressed by acid suppressants alone

Possible Effect of Concomitant Prokinetics and Herbal Medicines against Nausea in Patients Taking Lubiprostone

Background and Aim. Lubiprostone is a novel laxative that sometimes causes nausea, but preventive strategies remain unconfirmed. Methods. We retrospectively chose 126 patients prescribed lubiprostone from 2013 to 2016. Medical records were reviewed to clarify whether nausea developed after administration of the drug. Background characteristics, including concomitant medicines, were also reviewed. Results. The most common adverse symptom was diarrhea (23.8%). Nausea occurred in 16 patients (12.7%). Patients taking either prokinetics or herbal medicines or both were unlikely to develop nausea (p=0.007). Conclusions. Concomitant prokinetics and/or herbal medicines may help alleviate lubiprostone-induced nausea

Difference between the Upper and the Lower Gastrointestinal Bleeding in Patients Taking Nonvitamin K Oral Anticoagulants

Nonvitamin K oral anticoagulants (NOACs) sometimes cause hemorrhage, and the gastrointestinal tract is a common site of involvement. However, clinical characteristics of gastrointestinal bleeding (GIB) during NOAC therapy have not been fully elucidated. We studied 658 patients who were prescribed dabigatran, rivaroxaban, or apixaban between April 2011 and November 2015. Medical charts were reviewed to examine whether clinically relevant bleeding (Bleeding Academic Research Consortium criteria type 2 or greater) developed. The incidence of GIB was 2.0%/year, and one-third was from the upper GI. Among all hemorrhagic events, GIB was the most common cause. The extent of bleeding from the GI tract, particularly the upper GI tract, was more serious than bleeding from the other site. Multiple regression analysis showed that both past digestive ulcer and absence of concomitant proton pump inhibitors were significantly associated with the incidence of upper GIB, while concomitant nonsteroidal anti-inflammatory drugs, dual antiplatelets, and past GIB were significant factors regarding lower GIB. GIB was common and serious in patients taking NOACs. Upper GIB tended to become more serious than lower GIB. Proton pump inhibitors seem to be key drugs for preventing upper GIB during NOAC therapy

Current Treatment Results of Intracranial Carotid Artery Dissection Causing Cerebral Ischemia: A Japanese Nationwide Survey

Intracranial carotid artery dissection causing cerebral ischemia is a rare but important cause of cerebral infarction in children and adolescents. Although endovascular therapy has been reported to be effective, questions regarding the indications for intervention are yet to be addressed. Therefore, this study aimed to evaluate factors related to clinical outcomes through a nationwide survey. Overall, 35 neurosurgical centers reported patients within 2 weeks after ischemic onset due to intracranial carotid artery dissection causing cerebral ischemia treated between January 2015 and December 2020. Data on clinical and radiological findings were statistically analyzed. Twenty-eight patients met the inclusion criteria. The median age was 36 years (range, 7-59 years), without sex differences. Headache at onset was documented in 60.7% of the patients. Dissection findings were categorized into stenosis (71.4%) or occlusion (28.6%). Initial treatments, including various antithrombotic agent combinations in 23 (82.1%) patients, effectively improved or prevented aggravation in half of the patients. The patients with stenotic dissection were significantly more likely to experience aggravation during the initial treatment than did those with occlusive dissection (P = 0.03). In addition, the patients with moderate to severe neurological deficits on admission had poorer outcomes at discharge more frequently than did those with mild neurological deficits on admission. Eight patients undergoing endovascular therapy had no procedural complications or further aggravation after intervention. In conclusion, patients with intracranial carotid dissection causing cerebral ischemia who had a stenotic dissection were at risk of further aggravation, and endovascular therapy effectively improved or prevented aggravation

M-COPA suppresses endolysosomal Kit-Akt oncogenic signalling through inhibiting the secretory pathway in neoplastic mast cells

<div><p>Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs), acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib. Recently, we showed that in neoplastic mast cells that endogenously express an imatinib-resistant Kit mutant, Kit causes oncogenic activation of the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway and the signal transducer and activator of transcription 5 (STAT5) but only on endolysosomes and on the endoplasmic reticulum (ER), respectively. Here, we show a strategy for inhibition of the Kit-PI3K-Akt pathway in neoplastic mast cells by M-COPA (2-methylcoprophilinamide), an inhibitor of this secretory pathway. In M-COPA-treated cells, Kit localization in the ER is significantly increased, whereas endolysosomal Kit disappears, indicating that M-COPA blocks the biosynthetic transport of Kit from the ER. The drug greatly inhibits oncogenic Akt activation without affecting the association of Kit with PI3K, indicating that ER-localized Kit-PI3K complex is unable to activate Akt. Importantly, M-COPA but not imatinib suppresses neoplastic mast cell proliferation through inhibiting anti-apoptotic Akt activation. Results of our M-COPA treatment assay show that Kit can activate Erk not only on the ER but also on other compartments. Furthermore, Tyr568/570, Tyr703, Tyr721, and Tyr936 in Kit are phosphorylated on the ER, indicating that these five tyrosine residues are all phosphorylated before mutant Kit reaches the plasma membrane (PM). Our study provides evidence that Kit is tyrosine-phosphorylated soon after synthesis on the ER but is unable to activate Akt and also demonstrates that M-COPA is efficacious for growth suppression of neoplastic mast cells.</p></div