Adverse events in endoscopic ultrasound-guided choledochoduodenostomy with lumen-apposing metal stents: A systematic review and meta-analysis.

BACKGROUND AND AIM: Several meta-analyses have analyzed the technical and clinical success of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) by using lumen-apposing metal stents (LAMS) in malignant biliary obstruction, but those concerning adverse events (AEs) are scarce. The current systematic review and meta-analysis was conducted to evaluate the AEs after EUS-CDS with LAMS. METHODS: A comprehensive literature search of PubMed, Embase, Scopus, Web of Science, and the Cochrane Library was conducted for studies reporting the outcomes of EUS-CDS with LAMS. The main endpoints were the incidence of overall and specific AEs. Moreover, the stent dysfunction, and reintervention rates were evaluated independently. RESULTS: A total of 21 studies (n = 1438) were included in the final meta-analysis. The pooled rate of technical and clinical success was 93.5% (95% confidence interval [CI]: 91.3-95.1) and 88.0% (95% CI: 83.9-91.1), respectively. After EUS-CDS with LAMS, the pooled incidence of overall AEs was 20.1% (95% CI: 16.0-24.9). The estimated rate of early AEs was 10.6% (95% CI: 7.9-14.2), and late AEs was 11.2% (95% CI: 8.2-15.2). Infection/cholangitis was the commonest AE, with a pooled incidence of 6.1% (95% CI: 3.7-10.1). The estimated incidence of stent dysfunction and reintervention was 10.5% (95% CI: 7.5-14.4), and 12.1% (95% CI: 9.3-15.7), respectively. CONCLUSION: Despite with a high technical and clinical success rate, EUS-CDS with LAMS may be associated with overall AEs and stent dysfunction in one-fifth and one-tenth of cases, respectively. Further efforts are required to optimize its safety and long-term stent patency.

EUS-guided gastroenterostomy for gastric outlet obstruction: a comprehensive meta-analysis.

OBJECTIVE: A comprehensive meta-analysis was performed to evaluate the efficacy and safety of endoscopic ultrasound-guided gastroenterostomy (EUS-GE) for benign and malignant gastric outlet obstruction (GOO). MATERIAL AND METHODS: PubMed, Embase, Web of Science and Cochrane Library were searched to identify relevant studies. The primary outcomes evaluated technical success, clinical success, and adverse events (AEs). RESULTS: Twenty­six studies with 1493 patients were included in this meta-analysis. The pooled rates of technical success, clinical success, and overall AEs of EUS-GE were 94.0%, 89.9%, and 13.1%, respectively. Eight studies were included in the subgroup meta-analysis for comparative evaluation of EUS-GE and surgical gastroenterostomy (SGE), while seven studies were for EUS-GE and enteral stenting (ES). Compared with SGE, the pooled odds ratios (ORs) of technical success, clinical success, and overall AEs of EUS-GE were 0.17 (p = .003), 1.42 (p = .40), and 0.15 (p < .00001), respectively. When compared with ES, the above corresponding pooled ORs were 0.55 (p = .11), 2.64 (p < .0001), and 0.41 (p = .01), respectively. CONCLUSION: Although it is technically challenging, this largest meta-analysis indicates that EUS­GE has comparable and high technical and clinical success rates and hence a very effective minimally invasive procedure for GOO.

GPR Clutter Removal Based on Weighted Nuclear Norm Minimization for Nonparallel Cases.

Ground-penetrating radar (GPR) is an effective geophysical electromagnetic method for underground target detection. However, the target response is usually overwhelmed by strong clutter, thus damaging the detection performance. To account for the nonparallel case of the antennas and the ground surface, a novel GPR clutter-removal method based on weighted nuclear norm minimization (WNNM) is proposed, which decomposes the B-scan image into a low-rank clutter matrix and a sparse target matrix by using a non-convex weighted nuclear norm and assigning different weights to different singular values. The WNNM method's performance is evaluated using both numerical simulations and experiments with real GPR systems. Comparative analysis with the commonly used state-of-the-art clutter removal methods is also conducted in terms of the peak signal-to-noise ratio (PSNR) and the improvement factor (IF). The visualization and quantitative results demonstrate that the proposed method outperforms the others in the nonparallel case. Moreover, it is about five times faster than the RPCA, which is beneficial for practical applications.

Long-Term Exposure to SSRI Citalopram Induces Neurotoxic Effects in Zebrafish.

Residual antidepressants are of increasing concern worldwide, yet critical information on their long-term neurotoxic impacts on nontarget aquatic animals is lacking. Here, we investigated the long-term effects (from 0 to 150 days postfertilization) of the selective serotonin reuptake inhibitor citalopram (0.1-100 µg/L) on motor function, learning, and memory in zebrafish over two generations and explored the reversibility of the effect in F1 larvae. Unlike F0+ larvae, we found that F1+ larvae displayed decreased sensorimotor performance when continuously exposed to citalopram at 100 µg/L. No adverse effects were found in F1- larvae after they were transferred to a clean medium. Whole-mount immunofluorescence assays suggested that the motor impairments were related to axonal projections of the spinal motor neurons (MNs). For F0+ adults, long-term citalopram exposure mainly caused male-specific declines in motor, learning, and memory performance. Analysis of serotonergic and cholinergic MNs revealed no significant changes in the male zebrafish spinal cord. In contrast, the number of glutamatergic spinal MNs decreased, likely associated with the impairment of motor function. Additionally, treatment with 100 µg/L citalopram significantly reduced the number of dopaminergic neurons, but no significant neuronal apoptosis was observed in the adult telencephalon. Overall, this study provides neurobehavioral evidence and novel insights into the neurotoxic mechanisms of long-term citalopram exposure and may facilitate the assessment of the environmental and health risks posed by citalopram-containing antidepressant drugs.

Low doses and lifecycle exposure of waterborne antidepressants in zebrafish model: A survey on sperm traits, reproductive behaviours, and transcriptome responses.

Venlafaxine and citalopram have been commonly found in surface water and may disrupt fish reproduction, yet the long-term impact and the underlying mechanism are largely unknown. Here, zebrafish were exposed to 0.1-100 µg/L venlafaxine and citalopram for their entire life cycle from embryo to adult, respectively. After exposure for 180 days, the lowest observable effective concentration (LOEC) of venlafaxine and citalopram to significantly reduce the mean number of egg production in adults were 10 and 1 µg/L, respectively, whereas the fertilization rate displayed no significant changes. Further, we investigated the impacts of venlafaxine and citalopram in a reproductive context, including sperm quality and reproductive behaviour. In contrast, venlafaxine and citalopram exposure did not affect sperm quality but caused a reduction of reproductive behaviour (e.g., mating duration and mating interval) of adults exposed to 1-10 µg/L of the antidepressant. Transcriptomic profiling of the whole ovary revealed that lifecycle venlafaxine and citalopram exposure significantly affected the Na+/Cl- dependent neurotransmitter transporters signaling. Moreover, immune system-mediated ovarian regeneration and creatine metabolism regulated energy metabolism were proposed as the novel mechanism in the observed effects. Taken together, our results highlight the risk of lifecycle venlafaxine and citalopram exposure to fish reproduction and provide novel perspectives for unveiling the mechanism of female reproductive dysfunction.

Comparison of Choledochoduodenostomy and Hepaticogastrostomy for EUS-Guided Biliary Drainage: A Meta-Analysis.

Background: Although endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) or hepaticogastrostomy (EUS-HGS) has emerged as an option for patients of failed endoscopic retrograde cholangiopancreatography (ERCP), there has no agreement on which approach is preferred. Therefore, a meta-analysis was performed to examine the two methods. Methods: We performed a comprehensive search in databases of PubMed, Embase, and Cochrane library to find relevant studies reporting the efficacy and safety of the two EUS-guided biliary drainage methods. Results: In total, 12 studies with 623 patients (EUS-CDS: 303 and EUS-HGS: 320) were included. The cumulative technical success and clinical success for EUS-CDS and EUS-HGS was 95.0% (288/303), 93.1% (268/288), and 96.6% (309/320), 91.3% (282/309), respectively. Compared with EUS-HGS, the pooled odds ratio (OR) was 0.74 (95% CI 0.33-1.65; p = 0.46) for EUS-CDS technical success and 0.94 (95% CI 0.56-1.59; p = 0.83) for clinical success. The pooled difference in means of procedure time of EUS-CDS and EUS-HGS was -2.68 (95% CI -5.12 to -0.24; p = 0.03). The cumulative early adverse events for EUS-CDS and EUS-HGS was 12.2% (37/303) and 17.5% (56/320), respectively. Compared with EUS-HGS, the pooled OR of early adverse events for EUS-CDS was 0.58 (95% CI: 0.36-0.93; p = 0.02). Conclusion: This meta-analysis further suggests EUS-CDS and EUS-HGS have equal high technical and clinical success, but EUS-CDS with a slightly short procedure time and with less early adverse events compared to EUS-HGS.

Risks to aquatic environments posed by 14 pharmaceuticals as illustrated by their effects on zebrafish behaviour.

The presence of pharmaceutical residues in aquatic ecosystems is a worldwide problem that may pose serious threats and challenges to the environment, especially to the safety of aquatic biota. In the present study, we investigated the effects of 14 environmentally relevant pharmaceutical compounds on individual and collective-related behaviours in juvenile zebrafish (Danio rerio) for 21 days. The tested concentrations of the compounds spanned three orders of magnitude. This study also compared the potential risks of these compounds in Chinese surface waters based on the data on their toxic effects or only on behavioural effects. In the case of individual behaviours, most antidepressants, but not anti-inflammatory agents or blood lipid-lowering agents, decreased fish locomotor activity (LMA) and individual social activity (IDS); however, all three classes of compounds induced significant disruptions in the light/dark transition locomotor response (LMR-L/D) performance, even at lower treatment levels (0.1-1 µg/L). Furthermore, collective behaviour (CLB) analysis suggested that most of the compounds significantly altered the group sociability of fish and frequently occurred at environmentally relevant concentrations. Finally, a risk assessment suggested that the presence of ibuprofen, fluoxetine, and venlafaxine in the surface waters of China poses a relatively high risk to fish, regardless of the risk ranking based on the data of the toxic or behavioural effects.

Exosomes from EV71-infected oral epithelial cells can transfer miR-30a to promote EV71 infection.

OBJECTIVE: As an extracellular vesicle, exosomes can release from virus-infected cells containing various viral or host cellular elements and could stimulate recipient's cellular response. Enterovirus 71 (EV71), a single-strand positive-sense RNA virus, is known to cause hand, foot, and mouth disease (HFMD) in children and bring about severe clinical diseases. METHODS: Separated the human oral epithelial cells (OE cells) from normal buccal mucosa through enzyme digestion. Performed a comprehensive miRNA profiling in exosomes from EV71-infected OE cells through deep small RNA-seq. Using the Human Antiviral Response RT Profiler PCR Array profiles to explore the interactions of innate immune signaling networks with exosomal miR-30a. Knocked out the MyD88 gene in macrophages using CRISPR/Cas9-mediated genome editing method. RESULTS: Our study demonstrated that the miR-30a was preferentially enriched in exosomes that released from EV71-infected human oral epithelial cells through small RNA-seq. We found that the transfer of exosomal miR-30a to macrophages could suppress type Ⅰ interferon response through targeting myeloid differentiation factor 88 (MyD88) and subsequently facilitate the viral replication. CONCLUSIONS: Exosomes released from EV71-infected OE cells selectively packaged high level of miR-30a that can be functionally transferred to the recipient macrophages resulted in targeting MyD88 and subsequently inhibited type I interferon production in receipt cells, thus promoting the EV71 replication.

Predictive factors for extraction of common bile duct stones during endoscopic retrograde cholangiopancreatography in Billroth II anatomy patients.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) for extraction of common bile duct (CBD) stones in Billroth II anatomy patients is still a technical challenge and factors affecting stone extraction have not yet been clarified. This study aimed to analyze our experience and evaluate potential factors affecting CBD stone extraction. METHODS: A retrospective analysis of CBD stones patients with a history of Billroth II gastrectomy, who underwent therapeutic ERCP for stone extraction at our center from August 1999 to December 2017, was conducted. The outcomes of ERCP and potential factors affecting stone extraction were examined. RESULTS: A total of 227 patients were enrolled, and 176 patients (77.5%) achieved technical success. The success rate of duodenal ampullary access and selective biliary cannulation was 84.1% (191/227) and 92.1% (176/191), respectively. The mean CBD diameter was 15 mm (range 6-35 mm), and the largest stone size was 13 mm (range 4-36 mm). CBD stones were ultimately removed in 137 patients (77.8%), and 105 patients (59.7%) for the first session. Mechanical lithotripsy was used in 17 patients (9.7%). The overall ERCP-related complication rate was 6.3% (11/176), including bleeding in 3 patients (1.7%) and mild pancreatitis in 6 patients (3.4%). The multivariate analysis indicated that CBD stone number ≥ 2 (OR 2.171; 95% CI 1.095-4.306; p = 0.027), and the largest CBD stone size ≥ 12 mm (OR 3.646; 95% CI 1.833-7.251; p < 0.001) were patient-related risk factors for failed stone removal; while the use of endoscopic papillary (large) balloon dilation (EPBD/EPLBD) (OR 0.291; 95% CI 0.147-0.576; p < 0.001) was a procedure-related protective factor for successful stone extraction. CONCLUSIONS: ERCP is safe and effective for extraction of CBD stones in Billroth II anatomy patients. The number and the largest size of CBD stones, and the use of EPBD/EPLBD are predictive factors for CBD stone extraction.