Efficacy of GV1001 with gemcitabine/capecitabine in previously untreated patients with advanced pancreatic ductal adenocarcinoma having high serum eotaxin levels (KG4/2015): an open-label, randomised, Phase 3 trial.

BACKGROUND: The TeloVac study indicated GV1001 did not improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC). However, the cytokine examinations suggested that high serum eotaxin levels may predict responses to GV1001. This Phase III trial assessed the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated advanced PDAC. METHODS: Patients recruited from 16 hospitals received gemcitabine (1000 mg/m2, D 1, 8, and 15)/capecitabine (830 mg/m2 BID for 21 days) per month either with (GV1001 group) or without (control group) GV1001 (0.56 mg; D 1, 3, and 5, once on week 2-4, 6, then monthly thereafter) at random in a 1:1 ratio. The primary endpoint was overall survival (OS) and secondary end points included time to progression (TTP), objective response rate, and safety. RESULTS: Total 148 patients were randomly assigned to the GV1001 (n = 75) and control groups (n = 73). The GV1001 group showed improved median OS (11.3 vs. 7.5 months, P = 0.021) and TTP (7.3 vs. 4.5 months, P = 0.021) compared to the control group. Grade >3 adverse events were reported in 77.3% and 73.1% in the GV1001 and control groups (P = 0.562), respectively. CONCLUSIONS: GV1001 plus gemcitabine/capecitabine improved OS and TTP compared to gemcitabine/capecitabine alone in eotaxin-high patients with advanced PDAC. CLINICAL TRIAL REGISTRATION: NCT02854072.

Diagnostic Performance of Endoscopic Ultrasound Elastography for Differential Diagnosis of Gallbladder Polyp.

BACKGROUND AND AIMS: It is difficult to differentiate between neoplastic and non-neoplastic gallbladder (GB) polyps before surgery. Endoscopic ultrasound-elastography (EUS-EG) is a non-invasive complementary diagnostic method. The utility of EUS-EG in the differential diagnosis of GB polyps has not been investigated. We aimed to investigate the diagnostic performance of EUS-EG for the differential diagnosis of GB polyps. METHODS: Patients with GB polyps were prospectively enrolled from June 2020 until November 2022. EUS-EG and semi-quantitative evaluation of the strain ratio (SR) were performed for differential diagnosis of GB polyps. Fifty-three eligible patients were divided into two groups based on the final diagnosis after surgery. Patient demographics, EUS characteristics, and SR values were compared. Receiver-operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff SR value that discriminates between neoplastic and non-neoplastic GB polyps. RESULTS: The median SR value for neoplastic polyps (32.93 [interquartile range: 22.37-69.02]) was significantly higher than for non-neoplastic polyps (5.40 [2.36-14.44]; p<0.001). There were significant differences in SR values between non-neoplastic, benign neoplastic (23.38 [13.62-39.04]), and malignant polyps (49.25 [27.90-82.00]). The optimal cut-off SR value to differentiate between neoplastic and non-neoplastic polyps was 18.4. In multivariable logistic regression, SR value >18.4 (odds ratio 33.604, 95% confidence interval 2.588-436.292) was an independent predictor of neoplastic polyps. CONCLUSIONS: EUS-EG and SR values can be used as a supplementary method for evaluating GB polyps.

Development of a deep learning-based fully automated segmentation of rotator cuff muscles from clinical MR scans.

BACKGROUND: The fatty infiltration and atrophy in the muscle after a rotator cuff (RC) tear are important in surgical decision-making and are linked to poor clinical outcomes after rotator cuff repair. An accurate and reliable quantitative method should be developed to assess the entire RC muscles. PURPOSE: To develop a fully automated approach based on a deep neural network to segment RC muscles from clinical magnetic resonance imaging (MRI) scans. MATERIAL AND METHODS: In total, 94 shoulder MRI scans (mean age = 62.3 years) were utilized for the training and internal validation datasets, while an additional 20 MRI scans (mean age = 62.6 years) were collected from another institution for external validation. An orthopedic surgeon and a radiologist manually segmented muscles and bones as reference masks. Segmentation performance was evaluated using the Dice score, sensitivities, precision, and percent difference in muscle volume (%). In addition, the segmentation performance was assessed based on sex, age, and the presence of a RC tendon tear. RESULTS: The average Dice score, sensitivities, precision, and percentage difference in muscle volume of the developed algorithm were 0.920, 0.933, 0.912, and 4.58%, respectively, in external validation. There was no difference in the prediction of shoulder muscles, with the exception of teres minor, where significant prediction errors were observed (0.831, 0.854, 0.835, and 10.88%, respectively). The segmentation performance of the algorithm was generally unaffected by age, sex, and the presence of RC tears. CONCLUSION: We developed a fully automated deep neural network for RC muscle and bone segmentation with excellent performance from clinical MRI scans.

Biceps Rerouting Regardless of a Biceps-Labral Lesion During Rotator Cuff Repair Results in Lower Retear Rates and Comparable Clinical Outcomes to Subpectoral Biceps Tenodesis.

PURPOSE: To evaluate the radiographic and clinical outcomes when rerouting a pathologic biceps during arthroscopic rotator cuff repair by comparing it with concomitant subpectoral biceps tenodesis (SPBT). METHODS: This retrospective, historical cohort study was conducted with patients who underwent an arthroscopic repair of a full-thickness rotator cuff tear, with intraoperative confirmation of biceps pathology including partial tears, subluxation, pulley lesions, or type II SLAP lesions. Until May 2018, such patients were treated with concomitant subpectoral tenodesis (group SPBT). Afterward, biceps rerouting (BR) was done regardless of biceps pathology (group BR) without biceps or SLAP repair. Radiographic parameters, including fatty degeneration, acromiohumeral distance, Sugaya classification, and retears, were evaluated using preoperative and 1-year postoperative magnetic resonance imaging results. Clinical evaluation with a minimum 2-year follow-up included pain visual analog scale, American Shoulder and Elbow Surgeons, Simple Shoulder Test, and Constant-Murley scores. Whether individual patients exceeded these scores' minimal clinically important difference also was determined. RESULTS: A total of 64 patients (group SPBT = 32; group BR = 32) were included in the final analysis. The duration of clinical follow-up was 36.2 ± 9.3 months in group SPBT and 29.4 ± 6.9 months in the BR group (P = .002). Compared with group SPBT, group BR demonstrated a significantly lower retear rate (SPBT vs BR: 34.4% vs 12.5%, P = .039). In the BR group, 8 of 32 (25%) patients demonstrated a postoperative LHBT tear. The 4 cuff retears in group BR only took place within these patients. Other postoperative radiographic and clinical outcomes were comparable between the groups. Within each group, significant postoperative improvements were demonstrated (P < .05 for all clinical scores). CONCLUSIONS: Even in the presence of a pathologic LHBT and/or a type II SLAP lesion, augmenting the rotator cuff repair with BR significantly reduced retear rates while achieving clinical scores comparable with SPBT in a minimum 2-year follow-up. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Survival benefit of adjuvant treatment for ampullary cancer with lymph nodal involvement: A systematic review and meta-analysis.

BACKGROUND: The efficacy of adjuvant treatment (AT) in ampullary cancer (AmC) remains controversial. This systematic review and meta-analysis aimed to evaluate the role of AT for AmC. DATA SOURCES: A comprehensive systematic search was performed in PubMed, EMBASE, Cochrane Library, and Web of Science databases. Studies comparing overall survival (OS) and recurrence-free survival (RFS) of patients who underwent AT or not following AmC resection were included. RESULTS: A total of 3971 patients in 21 studies were analyzed. Overall pooled data showed no significant difference in effect on the OS by AT [hazard ratio (HR) = 0.998, 95% confidence interval (CI): 0.768-1.297]. No significant difference in recurrence between the AT and non-AT (nAT) groups was noted (HR = 1.158, 95% CI: 0.764-1.755). In subgroup analysis, patients who received AT showed favorable outcomes in the OS compared with those who received nAT in nodal-positive AmC (HR = 0.627, 95% CI: 0.451-0.870). Neither AT consisted of adjuvant chemotherapy with radiotherapy (HR = 0.804, 95% CI: 0.563-1.149) nor AT with adjuvant chemotherapy (HR = 0.883, 95% CI: 0.642-1.214) showed any significant effect on the OS. CONCLUSIONS: The effect of AT in AmC on survival and recurrence did not show a significant benefit. Furthermore, effectiveness according to AT strategies did not show enhancement in survival. AT had an advantage in survival compared with nAT strategy in nodal-positive AmC. In cases of AmC with positive lymph nodal involvement, AT may be warranted regardless of detailed strategies.

Effect of HY7602 Fermented Deer Antler on Physical Fatigue and Antioxidant Activity in Mice.

Lactobacillus curvatus HY7602 fermented antler (FA) ameliorates sarcopenia and improves exercise performance by increasing muscle mass, muscle fiber regeneration, and mitochondrial biogenesis; however, its anti-fatigue and antioxidant effects have not been studied. Therefore, this study aimed to investigate the anti-fatigue and antioxidant effects and mechanisms of FA. C2C12 and HepG2 cells were stimulated with 1 mM of hydrogen peroxide (H2O2) to induce oxidative stress, followed by treatment with FA. Additionally, 44-week-old C57BL/6J mice were orally administered FA for 4 weeks. FA treatment (5-100 µg/mL) significantly attenuated H2O2-induced cytotoxicity and reactive oxygen species (ROS) production in both cell lines in a dose-dependent manner. In vivo experiments showed that FA treatment significantly increased the mobility time of mice in the forced swimming test and significantly downregulated the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase (CK), and lactate. Notably, FA treatment significantly upregulated the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione/oxidized glutathione ratio (GSH/GSSG) and increased the mRNA expression of antioxidant genes (SOD1, SOD2, CAT, GPx1, GPx2, and GSR) in the liver. Conclusively, FA is a potentially useful functional food ingredient for improving fatigue through its antioxidant effects.

Transcriptome analysis of the endangered dung beetle Copris tripartitus (Coleoptera: Scarabaeidae) and characterization of genes associated to immunity, growth, and reproduction.

BACKGROUND: Dung beetles recycle organic matter through the decomposition of feces and support ecological balance. However, these insects are threatened by the indiscriminate use of agrochemicals and habitat destruction. Copris tripartitus Waterhouse (Coleoptera: Scarabaeidae), a dung beetle, is listed as a class-II Korean endangered species. Although the genetic diversity of C. tripartitus populations has been investigated through analysis of mitochondrial genes, genomic resources for this species remain limited. In this study, we analyzed the transcriptome of C. tripartitus to elucidate functions related to growth, immunity and reproduction for the purpose of informed conservation planning. RESULTS: The transcriptome of C. tripartitus was generated using next-generation Illumina sequencing and assembled de novo using a Trinity-based platform. In total, 98.59% of the raw sequence reads were processed as clean reads. These reads were assembled into 151,177 contigs, 101,352 transcripts, and 25,106 unigenes. A total of 23,450 unigenes (93.40%) were annotated to at least one database. The largest proportion of unigenes (92.76%) were annotated to the locally curated PANM-DB. A maximum of 5,512 unigenes had homologous sequences in Tribolium castaneum. Gene Ontology (GO) analysis revealed a maximum of 5,174 unigenes in the Molecular function category. Further, in Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, a total of 462 enzymes were associated with established biological pathways. Based on sequence homology to known proteins in PANM-DB, representative immunity, growth, and reproduction-related genes were screened. Potential immunity-related genes were categorized into pattern recognition receptors (PRRs), the Toll-like receptor signaling pathway, the MyD88- dependent pathway, endogenous ligands, immune effectors, antimicrobial peptides, apoptosis, and adaptation-related transcripts. Among PRRs, we conducted detailed in silico characterization of TLR-2, CTL, and PGRP_SC2-like. Repetitive elements such as long terminal repeats, short interspersed nuclear elements, long interspersed nuclear elements and DNA elements were enriched in the unigene sequences. A total of 1,493 SSRs were identified among all unigenes of C. tripartitus. CONCLUSIONS: This study provides a comprehensive resource for analysis of the genomic topography of the beetle C. tripartitus. The data presented here clarify the fitness phenotypes of this species in the wild and provide insight to support informed conservation planning.

A population-based cohort study on risk factors for acute pancreatitis: A comparison by age group.

BACKGROUND: /objectives: Acute pancreatitis (AP) is an acute inflammatory disorder that can occur in all age groups. The risk of AP has been shown to increase with age. However, no study has compared risk factors for AP according to age group yet. Thus, the aim of this study was to perform such comparison. METHODS: Clinical data from individuals 20 years of age and older who received a health examination arranged by the Korean national health insurance program in 2009 (n = 4,238,822) were used. First-attack AP was identified using claims data from baseline to December 2018. Incidence and risk factors of AP were analyzed for young (20-39 years old), middle-aged (40-64 years old), and old (over 65 years old) groups. RESULTS: Incidences of AP in young, middle-aged, and old groups were 16.30, 27.85, and 57.19 per 100,000 person-years, respectively. Smoking, alcohol drinking, diabetes, gallstone, and chronic pancreatitis were associated with increased risk of AP in all age groups. Meanwhile, male, older age, and higher waist circumference were associated with increased risk of AP in middle-aged and old groups. In young and middle-aged groups, risk of AP was increased in the presence of hypertension and dyslipidemia. However, high income was associated with decreased risk of AP in these groups. CONCLUSIONS: In this population-based cohort study, incidences and risk factors for AP differed according to age group. Thus, a tailored strategy might be needed to prevent AP according to age group.

Prolonged patency of fully covered self-expandable metal stents with an externally anchored plastic stent in distal malignant biliary obstruction.

BACKGROUND : Fully covered self-expandable metal stents (FCSEMSs) are widely used for endoscopic treatment of distal malignant biliary obstruction (dMBO). We aimed to assess the efficacy of anchoring an external plastic stent to an FCSEMS in dMBO. METHODS : A multicenter retrospective cohort study was performed in patients with dMBO to compare stent patency between FCSEMSs and FCSEMSs with an externally anchored plastic stent (EPS). For external anchoring, a 7-Fr double-pigtail plastic stent (DPPS) was placed first in the bile duct, then an FCSEMS was deployed side-by-side. RESULTS : Among a total of 185 patients, 65 had an FCSEMS alone and 120 had an FCSEMS with an EPS. The median stent patency was significantly longer in the FCSEMS with an EPS group than in the FCSEMS only group (342 vs. 240 days; P = 0.04). The rate of stent migration was significantly lower in the FCSEMS with an EPS group than in the FCSEMS only group (10.8 % vs. 27.7 %; P = 0.01). There were no significant differences in the rates of stent occlusion and adverse events between the two groups. CONCLUSIONS : A novel and simple technique of anchoring an external plastic stent may decrease the risk of FCSEMS migration and prolong stent patency, without significantly increasing the adverse events rate in dMBO.

The association between smoking, changes in smoking behavior, and acute pancreatitis: A population-based cohort study in Korea.

BACKGROUND AND AIMS: In the Asian population, existing studies regarding the association between smoking and acute pancreatitis are few in number. The aim of this study was to investigate the incidence of acute pancreatitis according to smoking habits and smoking habit changes of the Korean population. METHODS: We used clinical data from individuals (aged 20 years or older) who received health examinations arranged by the Korean National Health Insurance Service in 2009 (n = 4 238 822) or in 2009 and 2011 (n = 2 617 306). The incidence of acute pancreatitis was analyzed according to smoking status or smoking habit change reported by individuals during their health examination. Newly diagnosed acute pancreatitis was identified using claims data from baseline to the date of diagnosis or until December 31, 2018. RESULTS: The risk of acute pancreatitis was significantly higher in current smokers compared with never-smokers regardless of age or sex. The adjusted hazard ratio (HR) of acute pancreatitis in current smokers increased according to the amount of smoking (HR 1.28; 95% confidence interval [CI], 1.12-1.45 in <10 cigarettes/day, HR 1.4; CI, 1.3-1.52 in 10-19 cigarettes/day, HR 1.66; CI, 1.55-1.78 in ≥20 cigarettes/day). The adjusted HR of acute pancreatitis in continuous smokers was 1.66 (CI, 1.53-1.8) compared with never-smokers and was higher than smokers who quit smoking (HR 1.34; CI, 1.17-1.54). CONCLUSIONS: In this Korean population-based cohort study, smoking increased the incidence of acute pancreatitis in a dose-dependent manner, and smoking cessation helped decrease the incidence of acute pancreatitis.

Efficacy and predictive factors of endoscopic ultrasound-guided ethanol ablation in benign solid pancreatic tumors.

BACKGROUNDS AND OBJECTIVES: Endoscopic ultrasound-guided ethanol ablation (EUS-EA) has recently been introduced for the management of solid pancreatic tumors, including pancreatic neuroendocrine tumors (PNETs) and solid pseudopapillary tumors (SPTs). The study aims to evaluate the efficacy and predictive factors for response of EUS-EA in solid pancreatic tumors. METHODS: Between October 2015 and July 2021, 72 patients who underwent EUS-EA for solid pancreatic tumors were included. The study outcomes were to evaluate the efficacy of EUS-EA with complete remission (CR) and objective response, and their predictive factors. RESULTS: During follow-up, 47 patients were diagnosed with PNETs and 25 with SPTs. Eight cases reached CR and 48 reached objective response. When compared with SPTs, PNETs showed similar duration to reach CR (median not reached; p = 0.319), but shorter duration to reach objective response (PNETs: median 20.6 months, 95%CI 10.26-30.88; SPTs: median 47.7 months, 95%CI 18.14-77.20; p = 0.018). Ethanol dosage > 0.35 ml/cm3 shortened the duration to reach CR (median not reached; p = 0.026) and objective response (median 42.5 months, 95%CI 25.34-59.66 vs. 19.6 months, 95%CI 10.17-29.09; p = 0.006). CR had no significant predictive factors, but PNETs showed significant predictive factors for objective response (HR 3.34, 95%CI 1.07-10.43; p = 0.038). Twenty-seven patients experienced adverse events, and there were two severe cases. CONCLUSION: EUS-EA for pancreatic solid lesions seems feasible as a local treatment for patients who refuse or are unfit for surgery. Additionally, PNETs seem to be the better candidate for EUS-EA.

Usefulness of Liquid-Based Cytology in Diagnosing Biliary Tract Cancer Compared to Conventional Smear and Forceps Biopsy.

BACKGROUND/AIMS: Liquid-based cytology (LBC) has been shown to improve the diagnostic efficacy of brush cytology for thyroid, cervical and pancreatic cancer. To evaluate the diagnostic performance of LBC for biliary tract cancer, we compared it with conventional smears and forceps biopsies. METHODS: A retrospective study was conducted of all consecutive patients who underwent brush cytology under ERCP from January 2010 to April 2020. The primary outcome was the diagnostic efficacy of conventional smears and LBC. The difference between the two groups was corrected using inverse probability weighting (IPW). The secondary outcome was the sensitivity and specificity of brush cytology and forceps biopsy. The secondary outcome was evaluated in patients who underwent both methods. RESULTS: Among 162 patients, conventional smears were performed in 70 patients and LBC was performed in 92 patients. In the primary analysis using IPW, the sensitivity of conventional smears and LBC was 56.00% and 78.26% respectively (P = 0.009). The specificity was 100% for both methods. The accuracy was 66.15% for conventional smears and 83.33% for LBC (P = 0.012). In the secondary analysis, the sensitivity of conventional smears versus forceps biopsies was 62.16% versus 78.38% (P = 0.034) and 81.16% for both LBC and forceps biopsies. The specificity of both cytological examination and forceps biopsies was 100%. CONCLUSIONS: Liquid-based cytology demonstrated better sensitivity and accuracy than conventional smears. Moreover, its diagnostic performance was close to that of forceps biopsies.

Automatic Spine Segmentation and Parameter Measurement for Radiological Analysis of Whole-Spine Lateral Radiographs Using Deep Learning and Computer Vision.

Radiographic examination is essential for diagnosing spinal disorders, and the measurement of spino-pelvic parameters provides important information for the diagnosis and treatment planning of spinal sagittal deformities. While manual measurement methods are the golden standard for measuring parameters, they can be time consuming, inefficient, and rater dependent. Previous studies that have used automatic measurement methods to alleviate the downsides of manual measurements showed low accuracy or could not be applied to general films. We propose a pipeline for automated measurement of spinal parameters by combining a Mask R-CNN model for spine segmentation with computer vision algorithms. This pipeline can be incorporated into clinical workflows to provide clinical utility in diagnosis and treatment planning. A total of 1807 lateral radiographs were used for the training (n = 1607) and validation (n = 200) of the spine segmentation model. An additional 200 radiographs, which were also used for validation, were examined by three surgeons to evaluate the performance of the pipeline. Parameters automatically measured by the algorithm in the test set were statistically compared to parameters measured manually by the three surgeons. The Mask R-CNN model achieved an average precision at 50% intersection over union (AP50) of 96.2% and a Dice score of 92.6% for the spine segmentation task in the test set. The mean absolute error values of the spino-pelvic parameters measurement results were within the range of 0.4° (pelvic tilt) to 3.0° (lumbar lordosis, pelvic incidence), and the standard error of estimate was within the range of 0.5° (pelvic tilt) to 4.0° (pelvic incidence). The intraclass correlation coefficient values ranged from 0.86 (sacral slope) to 0.99 (pelvic tilt, sagittal vertical axis).

Effects of Ni/Al2O3 catalyst treatment condition on thermocatalytic conversion of spent disposable wipes.

Municipal solid waste (MSW) management is an essential municipal service. Proper waste treatment is an important part of the waste management. Thermocatalytic waste upcycling has recently gained great interest and attention as a method to extract value from waste, which potentially substitutes traditional waste treatment methods. This study aims at demonstrating the potential for thermocatalytic waste upcycling using spent disposable wipes as an MSW surrogate. Two different Ni/Al2O3 catalysts were prepared, treated under two different atmospheres (N2 and CO2). The catalyst treated in N2 (Ni/Al2O3-N2) exhibited a higher surface metallic Ni site than the catalyst treated in CO2 (Ni/Al2O3-CO2). The use of the Ni/Al2O3-N2 increased the yield of gas pyrolysate and decreased the yield of byproduct (e.g., wax), compared with no catalyst and the Ni/Al2O3-CO2. In particular, the Ni/Al2O3-N2 catalyst affected the generation of gaseous hydrogen (H2) by increasing the H2 yield by up to 102% in comparison with the other thermocatalytic systems. The highest H2 yield obtained with the Ni/Al2O3-N2 was attributed to the most surface metallic Ni sites. However, the Ni/Al2O3-N2 catalyst led to char having a lower higher heating value than the other catalysts due to its lowest carbon content. The results indicated that the reduction treatment environment for Ni/Al2O3 catalyst influences thermocatalytic conversion product yields of spent disposable wipes, including enhanced H2 production. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s11814-023-1461-8.

The effect of nafamostat mesilate infusion after ERCP for post-ERCP pancreatitis.

BACKGROUND: Nafamostat mesilate decreases the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, no studies have administered nafamostat mesilate after ERCP. So we investigated if the infusion of nafamostat mesilate after ERCP can affect the post-ERCP pancreatitis (PEP) in high-risk patients. METHODS: In a tertiary hospital, 350 high-risk patients of PEP were reviewed retrospectively. Among them, 201 patients received nafamostat mesilate after ERCP. Patient-related and procedure-related risk factors for PEP were collected. We performed a propensity score matching to adjust for the significant different baseline characteristics. The incidence and severity of PEP were evaluated according to the infusion of nafamostat mesilate. The risk factors of PEP were also analyzed by multivariate logistic regression. RESULTS: The baseline characteristics were not different after the matching. The PEP rate (17.4% vs. 10.3%, P = 0.141) was insignificant. Among the PEP patients, mild PEP was significantly higher in the nafamostat mesilate group (85.7% vs. 45.5%, P = 0.021). Only one patient in the nafamostat mesilate group developed severe PEP. Although young age (odds ratio [OR] 3.60, 95% CI 1.09-11.85, P = 0.035) was a risk factor, nafamostat mesilate (odds ratio [OR] 0.30, 95% CI 0.09-0.98, P = 0.047) was a protective factor for moderate to severe PEP. CONCLUSIONS: The administration of nafamostat mesilate after ERCP in high-risk patients was not effective in preventing PEP, but may attenuate the severity of PEP.

A Review on Fucoidan Structure, Extraction Techniques, and Its Role as an Immunomodulatory Agent.

Functional ingredients for human health have recently become the focus of research. One such potentially versatile therapeutic component is fucose-containing sulfated polysaccharides (FCSPs), referred to as fucoidans. The exploitation of marine brown algae provides a rich source of FCSPs because of their role as a structural component of the cell wall. Fucoidans are characterized by a sulfated fucose backbone. However, the structural characterization of FCSPs is impeded by their structural diversity, molecular weight, and complexity. The extraction and purification conditions significantly influence the yield and structural alterations. Inflammation is the preliminary response to potentially injurious inducements, and it is of the utmost importance for modulation in the proper direction. Improper manipulation and/or continuous stimuli could have detrimental effects in the long run. The web of immune responses mediated through multiple modulatory/cell signaling components can be addressed through functional ingredients, benefiting patients with no side effects. In this review, we attempted to address the involvement of FCSPs in the stimulation/downregulation of immune response cell signaling. The structural complexity and its foremost influential factor, extraction techniques, have also attracted attention, with concise details on the structural implications of bioactivity.

Acetylsalicylic acid for metal stent in malignant distal common bile duct obstruction: A randomized controlled trial.

BACKGROUND: Endoscopic biliary drainage is the treatment of choice for patients with malignant distal common bile duct obstruction. Self-expandable metal stents have clinical advantages including an increased duration of patency that may be prolonged by acetylsalicylic acid (ASA) use. The aim of this study was to investigate whether ASA had a positive effect on the patency of self-expandable metal stents compared with placebo. METHODS: This prospective, multicenter, double-blinded, and randomized placebo-controlled trial was conducted from October 2017 to May 2020 in Korea. Patients who underwent palliative endoscopic biliary drainage with self-expandable metal stents for malignant distal bile duct obstruction were enrolled, and allocated to ASA treatment or placebo. The study outcomes were the rate of stent dysfunction at 6 months, duration of stent patency, risk factors for stent dysfunction, and any adverse events. RESULTS: Interim analysis included 24 and 28 patients in the ASA and placebo groups, respectively. There was no significant difference between the ASA and placebo groups in stent dysfunction (25.0% vs. 20.7%, P = 0.761) or the duration of stent patency (150.97 ± 10.55 vs. 158.07 ± 8.70 days, P = 0.497). Six patients experienced suspected ASA-related adverse events, and there was one lethal case. CONCLUSIONS: ASA did not prolong stent patency. This study was terminated early because of the possibility of serious adverse events related to ASA treatment of these patients receiving palliative care.

Visualization of Transition Metal Decoration on h-BN Surface.

Functional h-BN (hexagonal boron nitride) has been prepared via the incorporation of transition metal (TM) impurities like nanoparticles and single atoms. Herein, scanning transmission electron microscopy (STEM) combined with density functional theory (DFT) was employed to study Ta-, Co-, Ni-, and Ir-decorated h-BN monolayers to provide an overview of their preferential site occupancies and morphological evolutions on h-BN. Ta, Ni, Ir, and Co single atoms are all positioned on the nitrogen of h-BN; however DFT predicts the occupancy site can vary with their spin state. In terms of microstructural evolution, Co, Ni, and Ir atoms form 3D nanoclusters while Ta atoms are well dispersed and thus the single Ta atom can be decorated on h-BN. This study highlights on TM/h-BN interaction dynamics and presents an avenue for designing nanostructures for electrocatalytic application.

Dieckol Inhibits Autophagic Flux and Induces Apoptotic Cell Death in A375 Human Melanoma Cells via Lysosomal Dysfunction and Mitochondrial Membrane Impairment.

Dieckol is a natural brown algal-derived polyphenol and its cytotoxic potential against various types of cancer cells has been studied. However, the effects of dieckol on autophagy in cancer cells remain unknown. Here, we show that dieckol inhibits the growth of A375 human melanoma cells by inducing apoptotic cell death, which is associated with lysosomal dysfunction and the inhibition of autophagic flux. Dieckol induces autophagosome accumulation by inhibiting autophagosome-lysosome fusion. Moreover, dieckol not only triggers lysosomal membrane permeabilization, followed by an increase in lysosomal pH and the inactivation of cathepsin B and D, but also causes the loss of mitochondrial membrane potential. Importantly, a cathepsin D inhibitor partially relieved dieckol-induced mitochondrial membrane impairment and caspase-mediated apoptosis. Collectively, our findings indicate that dieckol is a novel autophagy inhibitor that induces apoptosis-mediated cell death via lysosomal dysfunction and mitochondrial membrane impairment in A375 human melanoma cells. This suggests the novel potential value of dieckol as a chemotherapeutic drug candidate for melanoma treatment.

Tailoring Binding Abilities by Incorporating Oxophilic Transition Metals on 3D Nanostructured Ni Arrays for Accelerated Alkaline Hydrogen Evolution Reaction.

Developing efficient and inexpensive electrocatalysts for the hydrogen evolution reaction (HER) in alkaline water electrolysis plays a key role for renewable hydrogen energy technology. The slow reaction kinetics of HER in alkaline solutions, however, has hampered advances in high-performance hydrogen production. Herein, we investigated the trends in HER activity with respect to the binding energies of Ni-based thin film catalysts by incorporating a series of oxophilic transition metal atoms. It was found that the doping of oxophilic atoms enables the modulation of binding abilities of hydrogen and hydroxyl ions on the Ni surfaces, leading to the first establishment of a volcano relation between OH-binding energies and alkaline HER activities. In particular, Cr-incorporated Ni catalyst shows optimized OH-binding as well as H-binding energies for facilitating water dissociation and improving HER activity in alkaline media. Further enhancement of catalytic performance was achieved by introducing an array of three-dimensional (3D) Ni nanohelixes (NHs) that provide abundant surface active sites and effective channels for charge transfer and mass transport. The Cr dopants incorporated into the Ni NHs accelerate the dissociative adsorption process of water, resulting in remarkably enhanced catalytic activities in alkaline medium. Our approach can provide a rational design strategy and experimental methodology toward efficient bimetallic electrocatalysts for alkaline HER using earth-abundant elements.