Assessing risk stratification in long-term outcomes of rectal neuroendocrine tumors following endoscopic resection: a multicenter retrospective study.

OBJECTIVES: While endoscopic resection of rectal neuroendocrine tumors (NETs) has significantly increased, long-term data on risk factors for recurrence are still lacking. Our aim is to analyze the long-term outcomes of patients with rectal NETs after endoscopic resection through risk stratification. METHODS: In this multicenter retrospective study, we included patients who underwent endoscopic resection of rectal NETs from 2009 to 2018 and were followed for ≥12 months at five university hospitals. We classified the patients into three risk groups according to the clinicopathological status of the rectal neuroendocrine tumors: low, indeterminate, and high. The high-risk group was defined if the tumors have any of the followings: size ≥ 10 mm, lymphovascular invasion, muscularis propria or deeper invasion, positive resection margins, or mitotic count ≥2/10. RESULTS: A total of 346 patients were included, with 144 (41.6%), 121 (35.0%), and 81 (23.4%) classified into the low-, indeterminate-, and high-risk groups, respectively. Among the high-risk group, seven patients (8.6%) received salvage treatment 28 (27-67) days after the initial endoscopic resection, with no reported extracolonic recurrence. Throughout the follow-up period, 1.1% (4/346) of patients experienced extracolonic recurrences at 56.5 (54-73) months after the initial endoscopic resection. Three of these patients (75%) were in the high-risk group and did not undergo salvage treatment. The risk of extracolonic recurrence was significantly higher in the high-risk group compared to the other groups (p = 0.039). CONCLUSION: Physicians should be concerned about the possibility of metastasis during long-term follow-up of high-risk patients and consider salvage treatment.

Association between regular physical activity and lower incidence of colorectal cancer in patients with diabetes mellitus: a nationwide cohort study.

AIM: The aim of this work was to investigate the association between changes in physical activity (PA) status and the development of colorectal cancer (CRC) in patients with diabetes. METHOD: This nationwide population study included 1 439 152 patients with diabetes who underwent a health screening provided by the Korean National Health Insurance Service between January 2009 and December 2012 and a follow-up screening after 2 years. Based on changes in PA status, participants were categorized into four groups: remained inactive, remained active, active-to-inactive and inactive-to-active. RESULTS: During the median follow-up period of 5.2 years, 38 244 new cases of CRC were diagnosed. Compared with the remained inactive group, among the three other groups, the remained active group had the lowest risk of CRC [adjusted hazard ratio (aHR) 0.93; 95% CI 0.90-0.96], followed by the inactive-to-active group (aHR 0.97; 95% CI 0.94-1.00) and active-to-inactive group (aHR 0.99; 95% CI 0.96-1.02), after adjusting for confounding variables (p = 0.0007). This reduction in cancer incidence in the remained active group was observed for both rectal cancer (aHR 0.87, 95% CI 0.79-0.95) and colon cancer (aHR 0.93, 95% CI 0.90-0.97), irrespective of sex. In terms of the intensity and amount of PA, moderate intensity PA was the most effective, and a positive correlation was found between the amount of PA and the reduction in CRC incidence. CONCLUSION: Regular PA was independently associated with a decreased risk of CRC in patients with diabetes. The intensity and amount of physical activity both play a role in reducing the risk.

Five-year Progress of Gastric MALT Lymphoma Presenting as Gastric Outlet Obstruction.

This paper reports a 70-year-old female with gastric extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (gastric MALT lymphoma) as a rare case of gastric outlet obstruction. Five years earlier, she initially presented with weight loss and anemia. Esophagogastroduodenoscopy (EGD) revealed multiple gastric and duodenal ulcers with a pyloric deformity, while histology revealed chronic active inflammation and a Helicobacter pylori (H. pylori) infection. Three years earlier, she underwent EGD per the National Cancer Screening Program and was diagnosed with antral and duodenal ulcers. A forceps biopsy specimen from one of the ulcers showed the findings of gastric MALT lymphoma, but she did not visit the hospital for proper management. She visited complaining of a loss of appetite. EGD revealed a gastric outlet obstruction (GOO) caused by antral deformity and pyloric narrowing. A staged workup with CT and PET revealed full-layered, encircling antral wall thickening and several enlarged mesenteric lymph nodes. She was finally diagnosed with a gastric MALT lymphoma at Ann Arbor stage I1E with translocation t(11;18). She was treated with palliative surgery for GOO and systemic chemotherapy with a CHOP regimen. This paper reports a gastric MALT lymphoma that progressed from superficial mucosal lesions to an overt mass with regional lymph node metastasis for five years.

Quantitative multiplex real-time polymerase chain reaction assay for the detection of Helicobacter pylori and clarithromycin resistance.

BACKGROUND: Identifying clarithromycin resistance is essential for eradicating Helicobacter pylori (HP). Therefore, we evaluated the performance of Allplex™ H.pylori & ClariR Assay (Allplex™) for diagnosing and detecting clarithromycin resistance in HP. METHODS: Subjects who underwent esophagogastroduodenoscopy between April 2020 and August 2021 at Incheon St. Mary's hospital were enrolled in this study. The diagnostic performances of Allplex™ and dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) were compared with sequencing as the gold standard. RESULTS: A total of 142 gastric biopsy samples were analyzed. Gene sequencing revealed 124 HP infections, 42 A2143G mutations, 2 A2142G mutations, one dual mutation, and no A2142C mutation. DPO-PCR showed 96.0% sensitivity and 100.0% specificity for HP detection; the corresponding rates for Allplex™ were 99.2% and 100.0%. DPO-PCR showed 88.3% sensitivity and 82.0% specificity for A2143G mutation, and Allplex™ showed 97.6% and 96.0%. The Cohen's Kappa coefficient for overall test results was 0.56 for DPO-PCR and 0.95 for Allplex™. CONCLUSION: Allplex™ showed comparable diagnostic performance with direct gene sequencing and non-inferior diagnostic performance to DPO-PCR. Further research is required to confirm whether Allplex™ is an effective diagnostic tool for the eradication of HP.

The pattern of metachronous recurrence after endoscopic submucosal dissection for gastric adenocarcinoma and dysplasias.

BACKGROUND/AIMS: Metachronous recurrence incidences and risk factors following endoscopic submucosal dissection (ESD) for gastric adenocarcinoma and dysplasias were investigated. METHODS: Retrospective review of electronic medical records of patients who underwent gastric ESD at The Catholic University of Korea, Yeouido St. Mary's Hospital. RESULTS: A total of 190 subjects were enrolled for analysis during the study period. The mean age was 64.4 years-old and the male sex occupied 73.7%. The mean observation period following ESD was 3.45 years. The annual incidence rate of metachronous gastric neoplasms (MGN) was about 3.96%. The annual incidence rate was 5.36% for the low-grade dysplasia group, 6.47% for the high-grade dysplasia group, and 2.74% for the EGC group. MGN was more frequent in the dysplasia group than in the EGC group (p<0.05). For those with MGN development, the mean time interval from ESD to MGN was 4.1 (±1.8) years. By using the Kaplan-Meier model, the estimated mean MGN free survival time was 9.97 years (95% confidence interval, 8.53-11.40) The histological types of MGN were not related to the primary histology types. CONCLUSION: MGN following ESD developed in 3.96% annually and MGN was more frequent in the dysplasia group. The histological types of MGN did not correlate with those of primary neoplasm.

[Clinical Impact Assessment and Utilization Prospects of the t(11:18) Chromosomal Translocation in Gastric MALT Lymphoma in Koreans: A Single Center Retrospective Analysis].

Background/Aims: The gastric extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (gastric MALT lymphoma) are mostly related to Helicobacter pylori infections. However, chromosomal aberration involving translocation t(11;18) is also frequently reported in these patients. Methods: The study was a retrospective review and analysis of electronic medical records to assess the factors which affect complete remission (CR) in patients with gastric MALT lymphoma. Based on the medical records, subjects with gastric MALT lymphoma were enrolled consecutively from January 2004 to December 2021. Results: Among the 77 subjects who were found with gastric MALT lymphoma in the database, 65 cases with complete records were analyzed. Of these, 66.2% (43/65) were H. pylori positive. Genetic analyses for t(11:18) were done on 41 subjects. The t(11:18) chromosomal translocation with MALT1:BIRC3 fusion was found in 31.7% (13/41) of the subjects. With H. pylori eradication therapy, 75% (21/28) of the subjects without t(11:18) achieved CR. However, only 23.1% (3/13) subjects with t(11:18) could achieve CR (p-value= 0.009). In the H. pylori-positive group, 85.7% (18/21) subjects without t(11:18) achieved CR with eradication therapy, but 71.4% (5/7) subjects with t(11:18) failed to achieve CR (p-value=0.004). In the H. pylori-negative group, 42.3% (3/7) of the subjects without t(11:18) achieved CR with eradication therapy. However, 83.3% (5/6) of H. pylori-negative subjects with t(11:18) failed to achieve CR with eradication therapy and needed additional radiotherapy (p-value=0.396). Conclusions: H. pylori negativity and the presence of t(11:18) were both risk factors for failure to achieve CR with H. pylori eradication therapy as the first line of treatment.

Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis.

BACKGROUND: Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the K+/H+-ATPase enzyme in proton pumps within gastric parietal cells. Fexuprazan's suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner. AIM: To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE). METHODS: Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate of EE at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were compared between the groups. RESULTS: Of the 263 randomized, 218 completed the study per protocol (fexuprazan 40 mg, n = 107; esomeprazole 40 mg, n = 111). Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8 [99.1% (106/107) vs 99.1% (110/111)]. There were no between-group differences in the EE healing rate at week 4 [90.3% (93/103) vs 88.5% (92/104)], symptom responses, and quality of life assessments. Additionally, serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups. CONCLUSION: Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8. We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.

Factors associated with the risk of colorectal neoplasia in young adults under age 40.

BACKGROUND/AIMS: Recent epidemiologic studies have shown a continued increase in colorectal cancer incidence among younger adults. Little is known about the factors that contribute to the development of young-onset colorectal neoplasia (CRN). METHODS: A cross-sectional analysis was performed for individuals younger than 40 years who underwent colonoscopy in Seoul St. Mary's Hospital and its affiliated health screening center. High-risk CRN was defined as adenoma or sessile serrated lesion ≥ 10 mm, with three or more adenomas, villous histology, high grade dysplasia, or carcinoma. RESULTS: Of these 13,621 included participants, 2,023 (14.9%) had one and more CRN. Young patients with CRN tended to be elderly, male, obese, smoker, having a habit of drinking, and having comorbidities such as hypertension, dyslipidemia, diabetes, and chronic kidney disease. In a multivariate analysis adjusted for age, sex, obesity, smoking status, and alcohol intake, old age (odds ratio [OR], 1.086; 95% confidence interval [CI], 1.054 to 1.119), male sex (OR, 1.748; 95% CI, 1.247 to 2.451), obesity (OR, 1.439; 95% CI, 1.133 to 1.828), and smoking (OR, 1.654; 95% CI, 1.287 to 2.127) were independent risk factors for overall CRN. Obesity and smoking as two modifiable factors increased the risk for high-risk CRN even more than for overall CRN (OR, 1.734; 95% CI, 1.168 to 2.575 and OR, 1.797; 95% CI, 1.172 to 2.753, respectively). CONCLUSION: Obesity and smoking were modifiable risk factors for CRN in young adults. They increased the risk for highrisk CRN even more than for overall CRN. A colonoscopy might be beneficial for young individuals with these factors.

Feasibility of robotic thyroidectomy via hairline incision using da Vinci single port system: Initial experience with 40 consecutive cases.

BACKGROUND: This study aimed to introduce our robotic technique, which can minimize dissection extent using the da Vinci SP robotic system via hairline incision. METHODS: Forty patients underwent robotic thyroidectomy using the da Vinci SP robotic system via a hairline incision between February 2020 and April 2021 at Ulsan University Hospital. All procedures were performed successfully by one surgeon using the SP robotic system. RESULTS: Hemithyroidectomies were performed in 32 patients and total thyroidectomies in eight patients. Central neck dissection was performed in 32 patients. The overall mean operative time was 140.2 ± 50.7 min, and the mean console time was 74.0 ± 42.7 min. All patients were discharged on the second or third day after operation without any complications. CONCLUSIONS: Robotic thyroidectomy using the SP robotic system via hairline incision is technically feasible and safe, with a shorter incision length when compared with that of the Xi system.

[Factors Associated with the Clinical Outcomes of Iatrogenic Colonic Perforation].

Background/Aims: This study evaluated the incidence of iatrogenic colonic perforation (ICP) in a high-volume center and analyzed the clinical outcomes and associated factors. Methods: As a retrospective study of the electronic medical records, the whole data of patients who underwent colonoscopy from June 2004 to May 2020 were reviewed. Results: During 16 years, 69,458 procedures were performed, of which 60,288 were diagnostic and 9,170 were therapeutic. ICP occurred in 0.027% (16/60,288) for diagnostic colonoscopies and in 0.076% (7/9,170) for therapeutic purposes (p=0.015; hazard ratio 2.878; 95% CI, 1.184-6.997). Fifty-two percent (12 cases) were managed with endoscopic clip closure, and 43.5% (10 cases) required surgery. The reasons for the procedure and the procedure timing appeared to affect the treatment decision. Perforations during therapeutic colonoscopy were treated with surgery more often than those for diagnostic purposes (66.7% [4/6] vs. 37.5% [6/16], p=0.221). Regarding the timing of the procedure, ICP that occurred in the afternoon session was more likely treated surgically (56.3% [9/16] vs. 0/5, p=0.027). Mortality occurred in two patients (2/23, 8.7%). Both were aged (mean age 84.0±1.4 vs. 65.7±10.5, p<0.001) and lately recognized (mean elapsed time [hours], 43.8±52.5 vs. 1.5±3.0, p<0.001) than the surviving patients. Conclusions: ICP occurs in less than 0.1% of cases. The events that occurred during the morning session were more likely managed endoscopically. Age over 80 years and a longer time before perforation recognition were associated with mortality.

Molecular Detection of Parvovirus in Manchurian Chipmunks (Tamias sibiricus asiaticus) Captured in Korea.

Cross-species transmission of viral diseases alarms our global community for its potential of novel pandemic events. Of various viral pathogens noted recently, parvoviruses have posed public health threats not only to humans but also to wild animals. To investigate the prevalence of parvoviruses in wild Manchurian chipmunks, here we detected genetic fragments of the nonstructural protein of parvovirus by polymerase chain reaction in wild Manchurian chipmunk specimens captured in the central and southern regions of South Korea and compared their sequence homology with references. Of a total of 348 specimens examined, chipmunk parvovirus (ChpPV)-specific gene fragments were detected with a 31.32% rate (109 chipmunks of 348) in their kidney, liver, lung, and spleen samples, and the chipmunks captured in Gangwon Province exhibited the highest positive rate (45.37%), followed by Gyeongsang (35.29%), Gyeonggi (31.03%), Chungcheong (20.00%), and Jeolla (19.70%). When compared with the reference sequences, a partial ChpPV sequence showed 97.70% identity to the previously reported Korean strain at the nucleic acid level. In the phylogenetic analysis, ChpPV exhibited closer relationship to primate parvoviruses, erythroviruses, and bovine parvovirus than to adeno-associated viruses. Despite limited sample size and genetic sequences examined in this study, our results underline the prevalence of ChpPV in Korea and emphasize the need of close surveillance of parvoviruses in wild animals.

Convolutional neural network-based object detection model to identify gastrointestinal stromal tumors in endoscopic ultrasound images.

BACKGROUND AND AIM: We aimed to develop a convolutional neural network (CNN)-based object detection model for the discrimination of gastric subepithelial tumors, such as gastrointestinal stromal tumors (GISTs), and leiomyomas, in endoscopic ultrasound (EUS) images. METHODS: We used 376 images from 114 patients with histologically confirmed gastric GIST or leiomyoma to train the EUS-CNN. We constructed the EUS-CNN using an EfficientNet CNN model for feature extraction and a weighted bi-directional feature pyramid network for object detection. We assessed the performance of our EUS-CNN by calculating its accuracy, sensitivity, specificity, and area under receiver operating characteristic curve (AUC) using a validation set of 170 images from 54 patients. Four EUS experts and 15 EUS trainees were asked to judge the same validation dataset, and the diagnostic yields were compared between the EUS-CNN and human assessments. RESULTS: In the per-image analysis, the sensitivity, specificity, accuracy, and AUC of our EUS-CNN were 95.6%, 82.1%, 91.2%, and 0.9234, respectively. In the per-patient analysis, the sensitivity, specificity, accuracy, and AUC for our object detection model were 100.0%, 85.7%, 96.3%, and 0.9929, respectively. The EUS-CNN outperformed human assessment in terms of accuracy, sensitivity, and negative predictive value. CONCLUSIONS: We developed the EUS-CNN system, which demonstrated high diagnostic ability for gastric GIST prediction. This EUS-CNN system can be helpful not only for less-experienced endoscopists but also for experienced ones. Additional EUS image accumulation and prospective studies are required alongside validation in a large multicenter trial.

Antiviral Efficacy of Pralatrexate against SARS-CoV-2.

Novel coronavirus (SARS-CoV-2) has caused more than 100 million confirmed cases of human infectious disease (COVID-19) since December 2019 to paralyze our global community. However, only limited access has been allowed to COVID-19 vaccines and antiviral treatment options. Here, we report the efficacy of the anticancer drug pralatrexate against SARS-CoV-2. In Vero and human lung epithelial Calu-3 cells, pralatrexate reduced viral RNA copies of SARS-CoV-2 without detectable cytotoxicity, and viral replication was successfully inhibited in a dose-dependent manner. In a time-to-addition assay, pralatrexate treatment at almost half a day after infection also exhibited inhibitory effects on the replication of SARS-CoV-2 in Calu-3 cells. Taken together, these results suggest the potential of pralatrexate as a drug repurposing COVID-19 remedy.

The Potential Roles of Ghrelin in Metabolic Syndrome and Secondary Symptoms of Alzheimer's Disease.

Although the major causative factors of Alzheimer's disease (AD) are the accumulation of amyloid ß and hyperphosphorylated tau, AD can also be caused by metabolic dysfunction. The major clinical symptom of AD is cognitive dysfunction. However, AD is also accompanied by various secondary symptoms such as depression, sleep-wake disturbances, and abnormal eating behaviors. Interestingly, the orexigenic hormone ghrelin has been suggested to have beneficial effects on AD-related metabolic syndrome and secondary symptoms. Ghrelin improves lipid distribution and alters insulin sensitivity, effects that are hypothesized to delay the progression of AD. Furthermore, ghrelin can relieve depression by enhancing the secretion of hormones such as serotonin, noradrenaline, and orexin. Moreover, ghrelin can upregulate the expression of neurotrophic factors such as brain-derived neurotrophic factor and modulate the release of proinflammatory cytokines such as tumor necrosis factor α and interleukin 1ß. Ghrelin alleviates sleep-wake disturbances by increasing the levels of melatonin, melanin-concentrating hormone. Ghrelin reduces the risk of abnormal eating behaviors by increasing neuropeptide Y and γ-aminobutyric acid. In addition, ghrelin increases food intake by inhibiting fatty acid biosynthesis. However, despite the numerous studies on the role of ghrelin in the AD-related pathology and metabolic disorders, there are only a few studies that investigate the effects of ghrelin on secondary symptoms associated with AD. In this mini review, our purpose is to provide the insights of future study by organizing the previous studies for the role of ghrelin in AD-related pathology and metabolic disorders.

Sino-Cutaneous Fistula After Using Medpor Implant in Orbital Blowout Fracture.

In surgical repair of orbital fracture, implant materials play an important role in restoring the functional and anatomic structure of the orbit. Alloplastic implant materials are widely used for this surgery, but they have the risk of complications such as infections, pain, and extrusion. Because they are artificial implants, infection can occur more than autologous implants and is the most challenging problem to manage. Sino-cutaneous fistula is a rare complication of chronic sinusitis and it can be caused by this implant materials. The authors report a case of formation of sino-cutaneous fistula after using Medpor (Stryker Co, MI) implant in orbital blowout fracture repair.

Effect of Helicobacter pylori Treatment on Long-term Mortality in Patients with Hypertension.

Background/Aims: A meta-analysis of randomized trials performed in healthy asymptomatic individuals suggested that overall mortality may increase after Helicobacter pylori eradication despite a significant decrease in the gastric cancer incidence and mortality rates. This retrospective population-based cohort study investigated if H. pylori treatment is associated with an increase in overall mortality in patients with hypertension. Methods: From the database of the Korean National Health Insurance Sample Cohort, we selected 198,487 patients treated for hypertension between 2002 and 2010. Those who received H. pylori treatment (H. pylori treatment cohort, 5,541 patients) were matched to those who did not (nontreatment cohort, 11,082 patients) at the ratio of 1 to 2. The primary outcome was the risk of overall mortality. The secondary outcomes were the risks of mortality due to cardiovascular disease, cerebrovascular disease, and cancer. The outcomes were evaluated from 6 months after H. pylori treatment to December 2013. A Cox proportional hazard model was used to estimate the hazard ratios (HRs). Results: During a median follow-up period of 4.8 years, death from any cause was reported in 4.1% of the patients in the H. pylori treatment cohort and 5.5% of the patients in the nontreatment cohort. The adjusted HR (aHR) for overall mortality in the H. pylori treatment cohort was 0.70 (95% confidence interval [CI], 0.60 to 0.82; p<0.001). With regard to cause-specific mortality, compared with the nontreatment cohort, the H. pylori treatment cohort had a lower risk of mortality due to cerebrovascular disease (aHR, 0.46; 95% CI, 0.26 to 0.81; p=0.007). The risks of mortality due to cancer and cardiovascular disease were not different between the cohorts. Conclusions: H. pylori treatment is not associated with an increase in overall mortality in patients treated for hypertension.

Pharmacological Stimulation of Nurr1 Promotes Cell Cycle Progression in Adult Hippocampal Neural Stem Cells.

Nuclear receptor related-1 (Nurr1) protein performs a crucial role in hippocampal neural stem cell (hNSC) development as well as cognitive functions. We previously demonstrated that the pharmacological stimulation of Nurr1 by amodiaquine (AQ) promotes spatial memory by enhancing adult hippocampal neurogenesis. However, the role of Nurr1 in the cell cycle regulation of the adult hippocampus has not been investigated. This study aimed to examine changes in the cell cycle-related molecules involved in adult hippocampal neurogenesis induced by Nurr1 pharmacological stimulation. Fluorescence-activated cell sorting (FACS) analysis showed that AQ improved the progression of cell cycle from G0/G1 to S phase in a dose-dependent manner, and MEK1 or PI3K inhibitors attenuated this progression. In addition, AQ treatment increased the expression of cell proliferation markers MCM5 and PCNA, and transcription factor E2F1. Furthermore, pharmacological stimulation of Nurr1 by AQ increased the expression levels of positive cell cycle regulators such as cyclin A and cyclin-dependent kinases (CDK) 2. In contrast, levels of CDK inhibitors p27KIP1 and p57KIP2 were reduced upon treatment with AQ. Similar to the in vitro results, RT-qPCR analysis of AQ-administered mice brains revealed an increase in the levels of markers of cell cycle progression, PCNA, MCM5, and Cdc25a. Finally, AQ administration resulted in decreased p27KIP1 and increased CDK2 levels in the dentate gyrus of the mouse hippocampus, as quantified immunohistochemically. Our results demonstrate that the pharmacological stimulation of Nurr1 in adult hNSCs by AQ promotes the cell cycle by modulating cell cycle-related molecules.

Factors Associated with Rebleeding in Patients with Peptic Ulcer Bleeding: Analysis of the Korean Peptic Ulcer Bleeding (K-PUB) Study.

BACKGROUND/AIMS: Rebleeding is associated with mortality in patients with peptic ulcer bleeding (PUB), and risk stratification is important for the management of these patients. The purpose of our study was to examine the risk factors associated with rebleeding in patients with PUB. METHODS: The Korean Peptic Ulcer Bleeding registry is a large prospectively collected database of patients with PUB who were hospitalized between 2014 and 2015 at 28 medical centers in Korea. We examined the basic characteristics and clinical outcomes of patients in this registry. Univariate and multivariate analyses were performed to identify the factors associated with rebleeding. RESULTS: In total, 904 patients with PUB were registered, and 897 patients were analyzed. Rebleeding occurred in 7.1% of the patients (64), and the 30-day mortality was 1.0% (nine patients). According to the multivariate analysis, the risk factors for rebleeding were the presence of co-morbidities, use of multiple drugs, albumin levels, and hematemesis/hematochezia as initial presentations. CONCLUSIONS: The presence of co-morbidities, use of multiple drugs, albumin levels, and initial presentations with hematemesis/hematochezia can be indicators of rebleeding in patients with PUB. The wide use of proton pump inhibitors and prompt endoscopic interventions may explain the low incidence of rebleeding and low mortality rates in Korea.

Lin28B and miR-142-3p regulate neuronal differentiation by modulating Staufen1 expression.

Staufen1 (STAU1) and Lin28B are RNA-binding proteins that are involved in neuronal differentiation as a function of post-transcriptional regulation. STAU1 triggers post-transcriptional regulation, including mRNA export, mRNA relocation, translation and mRNA decay. Lin28B also has multiple functions in miRNA biogenesis and the regulation of translation. Here, we examined the connection between STAU1 and Lin28B and found that Lin28B regulates the abundance of STAU1 mRNA via miRNA maturation. Decreases in the expression of both STAU1 and Lin28B were observed during neuronal differentiation. Depletion of STAU1 or Lin28B inhibited neuronal differentiation, and overexpression of STAU1 or Lin28B enhanced neuronal differentiation. Interestingly, the stability of STAU1 mRNA was modulated by miR-142-3p, whose maturation was regulated by Lin28B. Thus, miR-142-3p expression increased as Lin28B expression decreased during differentiation, leading to the reduction of STAU1 expression. The transcriptome from Staufen-mediated mRNA decay (SMD) targets during differentiation was analyzed, confirming that STAU1 was a key factor in neuronal differentiation. In support of this finding, regulation of STAU1 expression in mouse neural precursor cells had the same effects on neuronal differentiation as it did in human neuroblastoma cells. These results revealed the collaboration of two RNA-binding proteins, STAU1 and Lin28B, as a regulatory mechanism in neuronal differentiation.