Disulfiram relieves severe acute pancreatitis by inhibiting GSDMD-dependent NETs formation.

OBJECTIVES: Severe acute pancreatitis (SAP) is characterized by pancreatic and systemic inflammation and persistent organ failure. Neutrophil extracellular traps (NETs) are considered to play an important role in the development of SAP. We aimed to explore the effect of disulfiram (DSL), a newly developed anti-inflammatory drug, on NETs in SAP. METHODS: A mouse model of SAP was induced by caerulein and lipopolysaccharide, and the mice were divided into the normal control group, the DSL group, the SAP group, and the SAP treated with 50 mg/kg (50DSLSAP) and 100 mg/kg DSL (100DSLSAP) groups, respectively. The severity of SAP was evaluated based on the morphological and biochemical changes. Gasdermin D (GSDMD) expression was evaluated in vivo and in vitro to verify the effect of DSL. Additionally, the expressions of NETs were also evaluated in vivo and in vitro in SAP with and without DSL treatment to explore the possible mechanism of DSL on SAP. RESULTS: Pancreatic inflammatory injury increased in the SAP group, which was alleviated by DSL. GSDMD, a protein related to the formation of NETs, increased in SAP. Expressions of NETs were also promoted in the in vivo SAP model and by phorbol myristate acetate (PMA) in vitro. Moreover, DSL inhibited the expressions of GSDMD and NETs in vivo. The results were further confirmed in the in vitro experiment. CONCLUSIONS: NETs are highly associated with inflammatory injury in SAP. DSL inhibits NETs formation by downregulating GSDMD, which in turn relieves the inflammation of SAP. Our study may provide a possible therapeutic target for SAP.

The risk of aspirin induced postoperative hemorrhage: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Current guidelines recommend aspirin maintenance for high-risk endoscopic procedures. Some Asian physicians noticed increasing postoperative bleeding in patients taking aspirin. We aimed to explore whether risk of postoperative hemorrhage due to aspirin differs in the East and the West. METHODS: PubMed, EMBASE and Cochrane library database were systematically reviewed. We only included trials that met our criteria. RESULTS: There is significant association between aspirin and postoperative bleeding (P < 0.001), especially in Eastern population (data from Japan, Korea, Turkey and China, P < 0.001). Result from the West (data from America, Canada and Australia) had no statistical significance (P = 0.07). For Easterners, aspirin increased bleeding risk after endoscopic submucosal dissection (ESD) and endoscopic sphincterotomy (EST). For Westerners, aspirin increased bleeding risk post endoscopic mucosal resection (EMR). For patients undergoing ESD, those who continued to receive aspirin had higher bleeding risk than patients who interrupted it for more than 7 days (P = 0.005). CONCLUSION: Aspirin increases risk of postoperative hemorrhage. Easterners are more likely to suffer from bleeding after aspirin administration than Westerners. Stopping aspirin for more than 7 days may be advisable to control bleeding post ESD for patients with low risk of thrombosis.

Actual pressure generated by various suction technique and suctioning liquid weight through endoscopic ultrasound-guided aspiration needles.

OBJECTIVES: Suction pressure is one of the most important factors influencing the amount of tissue obtained during endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB). In this study we aimed to elucidate actual suction pressure generated by various suction methods and the weight of suctioning liquid. METHODS: Different types of fine needles and suction techniques were used, including the slow pull technique (SPT), dry suction technique (DST), wet suction technique (WST), neutralizing negative pressure technique (NNPT), and residual negative pressure technique (RNPT). Actual suction pressure was measured and the amount of suctioning liquid was weighed. RESULTS: Actual suction pressure and weight of the suctioning liquid were lower using SPT than using DST, while they were higher when using WST compared with those using DST. In general, the actual suction pressure increased and the weight of suctioning liquid decreased as the diameter of the FNA needles decreased. While weight of the suctioning liquid using FNB needles was significantly larger than that using FNA needles. In general, the actual suction pressure generated using RNPT was larger than that using NNPT. CONCLUSIONS: WST is superior to SPT and DST in terms of actual suction pressure and weight of suctioning liquid. Diameter of the FNA needle was an important factor that may affect the actual suction pressure and weight of suctioning liquid. FNB needles are superior to FNA needles when it comes to the weight of suctioning liquid. Actual suction pressure obtained by novel suction methods (NNPT and RNPT) may provide a basis for future research.

Identification of potential serum exosomal microRNAs involved in acinar-ductal metaplasia that is a precursor of pancreatic cancer associated with chronic pancreatitis.

BACKGROUNDS: Due to difficulty in early diagnosis of chronic pancreatitis (CP), it is urgent to find novel biomarkers to detect CP. Exosomal microRNAs (Exo-miRNAs) located in the serum may be potential diagnostic and therapeutic targets for CP. OBJECTIVE: To identify differentially expressed Exo-miRNAs (DE-Exo-miRNAs) in the serum of CP patients, we performed a bioinformatics analysis. METHODS: The dataset GSE128508 was downloaded from the Gene Expression Omnibus (GEO) database. The analysis was carried out using BRB-ArrayTools and significance analysis of microarrays (SAM). The target genes of DE-S-Exo-miRNAs were predicted by miRWalk databases. Further gene ontology (GO) term and Kyoto Encyclopedia of Genomes (KEGG) pathway analyses were performed with plug-in ClueGO in Cytoscape software 3.7.0. Subsequently, the interaction regulatory network between encoded proteins of target genes was performed with the Search Tool for the Retrieval of Interacting Genes (STRING) database and analyzed using plug-in Molecular Complex Detection (MCODE) and cytoHubba in Cytoscape software 3.7.0. RESULTS: We identified 227 DE-Exo-miRNAs in the serum. Further analysis using the miRWalk database identified 5164 target genes of these miRNAs. The protein-protein interaction (PPI) regulatory network of 1912 potential target genes for hub 10 up-regulated miRNAs with high degrees and one down-regulated miRNAs were constructed using the STRING database and Cytoscape software. The functional analysis using Cytoscape software tool highlighted that target genes involved in pancreatic cancer. Acinar-ductal metaplasia (ADM) in the inflammatory environment of CP is a precursor of pancreatic cancer. Subsequently, we constructed a network of target genes associated with ADM and their miRNAs. CONCLUSIONS: Exo-miRNAs in the serum as well as their target genes may be promising targets for the early diagnosis and treatment of CP. In addition, we identified potential Exo-miRNAs involved in ADM that is a precursor of pancreatic cancer associated with CP.

Improving the discomfort and satisfaction of colonoscopy by distraction with smartphones: A prospective randomized controlled study.

BACKGROUND: Colonoscopy is an uncomfortable procedure. Distraction is thought to reduce pain by decreasing the amount of attention a person spends on a painful stimulus. We aimed to assess the usefulness of smartphones on discomfort associated with the colonoscopy. METHODS: We designated 360 enrolled patients according to prospective randomized controlled study into two groups, including smartphone (SP) group (Relaxation by smartphones) and Control group (No relaxation). Measured outcomes included the discomfort, satisfaction, polyp detection rate and the willingness to repeat colonoscopy were analyzed between groups. RESULTS: The pain and distension scores of SP group patients were significantly lower than those of the Control group (2.18 ±â€Š2.80 vs 3.55 ±â€Š3.07, P < .001; 4.15 ±â€Š2.35 vs 4.79 ±â€Š2.36, P = .011, respectively). Importantly, patient-reported satisfaction scores of the SP group were significantly higher than those of the Control group (96.45 ±â€Š7.17 vs 91.12 ±â€Š10.49, respectively; P < .001). Moreover, although there were no statistical differences, patients using smartphones were more likely to have shorter reach cecum times (09m:11 s vs 07m:37 s, P = .116) and more polyp detection rate (13.3% vs 9.4%, P = .246). In addition, more patients using smartphones were willing to repeat colonoscopy but no statistical difference (85.0% vs 81.7%, P = .396). CONCLUSION: Patient using smartphone is a special manner to increase satisfaction during colonoscopy with a less discomfort and is more likely to be polyp detection rate.

Predictors of pain response after endoscopic ultrasound-guided celiac plexus neurolysis for abdominal pain caused by pancreatic malignancy.

BACKGROUND: Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) has gained popularity as a minimally invasive approach and is currently widely used to treat pancreatic cancer-associated pain. However, response to treatment is variable. AIM: To identify the efficacy of EUS-CPN and explore determinants of pain response in EUS-CPN for pancreatic cancer-associated pain. METHODS: A retrospective study of 58 patients with abdominal pain due to inoperable pancreatic cancer who underwent EUS-CPN were included. The efficacy for palliation of pain was evaluated based on the visual analog scale pain score at 1 wk and 4 wk after EUS-CPN. Univariable and multivariable logistic regression analyses were performed to explore predictors of pain response. RESULTS: A good pain response was obtained in 74.1% and 67.2% of patients at 1 wk and 4 wk, respectively. Tumors located in the body/tail of the pancreas and patients receiving bilateral treatment were weakly associated with a good outcome. Multivariate analysis revealed patients with invisible ganglia and metastatic disease were significant factors for a negative response to EUS-CPN at 1 wk and 4 wk, respectively, particularly for invasion of the celiac plexus (odds ratio (OR) = 13.20, P = 0.003 for 1 wk and OR = 15.11, P = 0.001 for 4 wk). No severe adverse events were reported. CONCLUSION: EUS-CPN is a safe and effective form of treatment for intractable pancreatic cancer-associated pain. Invisible ganglia, distant metastasis, and invasion of the celiac plexus were predictors of less effective response in EUS-CPN for pancreatic cancer-related pain. For these patients, efficacy warrants attention.

Watching Videos of Colonoscopies and Receiving Interpretations Reduce Pain and Anxiety While Increasing the Satisfaction of Patients.

BACKGROUND: Pain associated with colonoscopies is a major barrier to patients participating in colorectal cancer screenings. While sedation and analgesia are used to reduce pain during the procedure, they are associated with increased complications and costs. Thus, it is necessary to identity novel techniques to relieve pain in a safe and cost-effective way. AIMS: To test whether watching real-time videos of colonoscopies while receiving detailed interpretations of the procedures reduces pain and anxiety and increases a patient's satisfaction. METHODS: Patients were randomized into three groups including a group who watched real-time videos of their colonoscopies (Group A), a group who watched real-time videos of their colonoscopies while receiving detailed interpretations of the procedures from the endoscopists (Group B), and a group who did not receive either method (Group C). RESULTS: Pain and anxiety scores were significantly (Group A vs. Group C, [Formula: see text]; Group B vs. Group C, [Formula: see text]) lower in Groups A and B compared to Group C. Additionally, significantly (Group A vs. Group C, [Formula: see text]; Group B vs. Group C, [Formula: see text]) increased satisfaction was observed in Groups A and B compared to Group C. There were no statistically significant differences observed in the pain and anxiety scores when comparing Groups A and B. However, the overall satisfaction score was significantly ([Formula: see text]) higher in Group B compared to Group A. CONCLUSIONS: Real-time videos of colonoscopies as well as videos along with detailed interpretations of the procedures decrease pain and anxiety while improving satisfaction in patients undergoing colonoscopies without sedation. Videos combined with interpretations lead to a greater increase in patient satisfaction.

Exploration of an effective training system for the diagnosis of pancreatobiliary diseases with EUS: A prospective study.

BACKGROUND AND OBJECTIVE: There are limited data on multistage-based training programs focused on EUS. We aimed to explore an effective training system for diagnosing pancreaticobiliary diseases with EUS. MATERIALS AND METHODS: Nine advanced endoscopy trainees (AETs) with less EUS experience from nine institutions were recruited. The training system consisted of multiple stages and multi-teaching methods, including biliopancreatic standard scanning, anatomy and imaging knowledge, simulator, hands-on operations, error correction, and case analysis over a 12-month training period. Grading for technical and cognitive skills was assessed using The EUS Skills Assessment Tool. RESULTS: After training, the overall scores for radial (4.16 ± 0.21 vs. 1.46 ± 0.16, P < 0.01) and linear (4.43 ± 0.20 vs. 1.63 ± 0.23, P < 0.01) scanning were significantly improved. The aortopulmonary window/mediastinum station can be learned more easily by AETs compared with other stations (P = 0023). The scanning of the descending part of the duodenum seemed to improve the slowest after training (P = 0.0072), indicating that the descending part of the duodenum can be more difficult and should be the focus of training. Every teaching method heightened EUS competence, especially case analysis and hands-on operations. AETs achieved equivalent EUS competence after training despite their initial experience. Through a poststudy questionnaire, it was found that all AETs strongly agreed they were satisfied with the training system, and their confidence was greatly enhanced when EUS was performed independently. CONCLUSIONS: The current multistage and multi-methods training system showed efficient performance in the cognitive and technical competence of EUS. Descending part of duodenum scanning was difficult for beginners and should be the focus of training.