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Abstract Endoscopic ultrasound-guided fine needle biopsy is an effective method for obtaining tissue samples from various organs; however, challenges such as inadequate specimens persist. This study compared a newly designed Tricore needle with a Franseen needle for endoscopic ultrasound-guided fine needle biopsy of porcine liver. Both needles were tested on four male Yorkshire pigs. Specimens were obtained with an 100% (36/36) success rate with no procedure-related adverse effects. The Tricore needle experienced significantly less resistance during puncture than Franseen needle (3.83 vs. 5.97 N, P

Biliary strictures are characterized by the narrowing of the bile duct lumen, usually caused by surgical biliary injury, cancer, inflammation, and scarring from gallstones. Endoscopic stent placement is a well-established method for the management of biliary strictures. However, maintaining optimal mechanical properties of stents and designing surfaces that can prevent stent-induced tissue hyperplasia and biofilm formation are challenges in the fabrication of biodegradable biliary stents (BBSs) for customized treatment. This study proposes a novel approach to fabricating functionalized polymer BBSs with nanoengineered surfaces using 3D printing. The 3D printed stents, fabricated from bioactive silica poly(ε-carprolactone) (PCL) via a sol–gel method, exhibited tunable mechanical properties suitable for supporting the bile duct while ensuring biocompatibility. Furthermore, a nanoengineered surface layer was successfully created on a sirolimus (SRL)-coated functionalized PCL (fPCL) stent using Zn ion sputtering-based plasma immersion ion implantation (S-PIII) treatment to enhance the performance of the stent. The nanoengineered surface of the SRL-coated fPCL stent effectively reduced bacterial responses and remarkably inhibited fibroblast proliferation and initial burst release of SRL in vitro systems. The physicochemical properties and biological behaviors, including in vitro biocompatibility and in vivo therapeutic efficacy in the rabbit bile duct, of the Zn-SRL@fPCL stent demonstrated its potential as a versatile platform for clinical applications in bile duct tissue engineering.

Abstract ATP-binding cassette transporter B6 (ABCB6), a protein essential for heme biosynthesis in mitochondria, also functions as a heavy metal efflux pump. Here, we present cryo-electron microscopy structures of human ABCB6 bound to a cadmium Cd(II) ion in the presence of antioxidant thiol peptides glutathione (GSH) and phytochelatin 2 (PC2) at resolutions of 3.2 and 3.1 Å, respectively. The overall folding of the two structures resembles the inward-facing apo state but with less separation between the two halves of the transporter. Two GSH molecules are symmetrically bound to the Cd(II) ion in a bent conformation, with the central cysteine protruding towards the metal. The N-terminal glutamate and C-terminal glycine of GSH do not directly interact with Cd(II) but contribute to neutralizing positive charges of the binding cavity by forming hydrogen bonds and van der Waals interactions with nearby residues. In the presence of PC2, Cd(II) binding to ABCB6 is similar to that observed with GSH, except that two cysteine residues of each PC2 molecule participate in Cd(II) coordination to form a tetrathiolate. Structural comparison of human ABCB6 and its homologous Atm-type transporters indicate that their distinct substrate specificity might be attributed to variations in the capping residues situated at the top of the substrate-binding cavity.

BackgroundSleep problem is a common complication of Alzheimer’s disease (AD). Extensive preclinical studies have been performed to investigate the AD pathology. However, the pathophysiological consequence of AD complicated by sleep problem remains to be further determined.PurposeTo investigate brain metabolism and perfusion in an AD mouse model complicated by sleep problem, and subsequently identify potential imaging markers to better understand the associated pathophysiology.MethodsWe examined the oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen (CMRO2), and cerebral blood flow (CBF) using state-of-the-art MRI techniques in a cohort of 5xFAD model mice. Additionally, neuroinflammation, indicated by activated microglia, was assessed using histology techniques. Sleep fragmentation (SF) was utilized as a representative for sleep problems.ResultsSF was associated with significant increases in OEF (P = 0.023) and CMRO2 (P = 0.029), indicating a state of hypermetabolism. CBF showed a significant genotype-by-sleep interaction effect (P = 0.026), particularly in the deep brain regions such as the hippocampus and thalamus. Neuroinflammation was primarily driven by genotype rather than SF, especially in regions with significant interaction effect in CBF measurements.ConclusionThese results suggest that brain metabolism and perfusion measurements are promising markers for studying the co-pathogenesis of AD and SF.

Radiofrequency ablation (RFA) is a local treatment modality for primary liver cancers. Although various input parameters of the RF generator have been adjusted to improve the ablation ranges, the limited ablation ranges remain an obstacle to RFA. This study aimed to compare the ablation ranges and efficacy of sine and square electrical waveforms in a mouse tumor model. An RF generator with an adjustable electrical waveform was developed, and its ablation range in the porcine liver was compared. For all RF parameters, the square electrical waveform ablation range was greater than that of the sine electrical waveform (all p < 0.001) in the porcine liver. The 45 BALB/c nude mice were used to evaluate the efficacy of the two electrical waveforms after the RFA. The mean tumor volume in the square group was significantly lower than that in the sine group (p < 0.001), indicating a higher survival rate (60%). The cellular coagulative necrosis, inflammatory cell infiltration, heat shock proteins, cellular necrosis, and tumor necrosis were significantly greater in square electrical waveform than in sine electrical waveform (all; p < 0.05). RFA with square electrical waveforms has therapeutic potential for tumor management with an enhanced ablation range.

Background/Aims: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is essential in diagnosing solid pancreatic lesions (SPLs), but without rapid on-site evaluation (ROSE), a repeat EUS-FNA/B is crucial for clarifying an inconclusive diagnosis. We aimed to evaluate factors associated with improved diagnostic performance of repeat EUS-FNA/B for initially inconclusive SPL diagnoses without ROSE. Methods: Of 5,894 patients subjected to EUS-FNA/B, 237 (4.0%) with an initially inconclusive diagnosis of SPLs were retrospectively enrolled from five tertiary medical centers between January 2016 and June 2021. Diagnostic performance and procedural factors of EUS-FNA/B were analyzed. Results: The diagnostic accuracies of first and repeat EUS-FNA/B were 96.2% and 67.6%, respectively. Of 237 patients with an inconclusive diagnosis from initial EUS-FNA/B, 150 were pathologically diagnosed after repeat EUS-FNA/B. In multivariate analysis of repeat EUS-FNA/B, tumor location (body/tail vs head: odds ratio [OR], 3.74; 95% confidence interval [CI], 1.48 to 9.46), number of needle passes (≥4 vs ≤3: OR, 4.80; 95% CI, 1.44 to 15.99), needle type (FNB vs FNA: OR, 3.26; 95% CI, 1.44 to 7.36), needle size (22 gauge vs 19/20 gauge: OR, 2.35; 95% CI, 1.19 to 4.62), and suction method (suction vs others: OR, 5.19; 95% CI, 1.30 to 20.75) were associated with a significantly improved diagnostic performance. Conclusions: Repeat EUS-FNA/B is essential for patients with an inconclusive EUS-FNA/B without ROSE. To improve the diagnostic performance of repeated EUS-FNA/B, it is recommended that 22-gauge FNB needles, ≥4 needle passes, and suction methods are used.

Background/Aims: Acute-on-chronic liver failure (ACLF) is a widely recognized concept in which acute decompensation (AD) in patients with cirrhosis results in organ failure and high short-term mortality. On the other hand, few studies reflecting the various etiologies of cirrhosis are available. This study examined the clinical features of patients with hepatitis C virus (HCV)-related ACLF. Methods: Between January 2005 and December 2018, 109 HCV-related cirrhosis patients hospitalized for AD (ascites, hepatic encephalopathy, gastrointestinal hemorrhage, and bacterial infection) were enrolled for ACLF defined by the European Association for the Study of the Liver (EASL). Results: ACLF developed in 35 patients (32.1%) on admission. Eight, eight, and 19 patients had ACLF grades 1, 2, and 3, respectively. The 28-day and 90-day mortality rates were very low (2.7% and 5.4%, respectively) in patients without ACLF and very high (60.0% and 74.3%, respectively) in those with ACLF. In patients with HCV-related ACLF, compared to previous studies on hepatitis B virus-related ACLF and alcohol-related ACLF, the prevalence of liver failure was very low (17.1%), whereas that of kidney failure was very high (71.4%). Compared with all other prognostic scores, the Chronic liver failure Consortium Organ Failure score predicted the 90-day mortality most accurately, with an area under the receiver operator characteristic of 0.921. Conclusions: HCV-related ACLF has unique clinical characteristics distinct from hepatitis B virus-related and alcohol-related ACLF. ACLF defined by EASL can be useful for predicting the short-term mortality in HCV-related cirrhosis.

Despite the inhibitory effect of phytoncide (Pht) on food-borne pathogenic bacterial growth, the hydrophobic nature and susceptibility to biodegradation under physiological conditions limits its applications. Here, we developed Pht-loaded polyvinylpyrrolidone (PVP) micelles (Pht@PVP MC) via micelle packing. Pht was solubilized using different types of PVP as micellar vehicles. The as-prepared Pht@PVP MCs were characterized using dynamic light scattering and transmission electron microscopy. The sizes of the Pht@PVP MCs were controlled from 301 ± 51 to 80 ± 3 nm by adjusting the PVP content. The polydispersity index of Pht@PVP MC was between 0.21 ± 0.03 and 0.16 ± 0.04, indicating homogeneous size. A colony-counting method was employed to evaluate the improvement in antibacterial activity after Pht encapsulation in PVP micelles. The reactive oxygen species (ROS)-scavenging activity and anti-inflammatory efficacy of Pht@PVP MC were analyzed in a concentration range of 10–100 μg/mL by evaluating in vitro ROS and nitric oxide levels using DCFDA and Griess reagents. PVP with both hydrophobic and hydrophilic moieties improved the aqueous solubility of Pht and stabilized it via steric hindrance. Higher-molecular-weight PVP at higher concentrations resulted in a smaller hydrodynamic diameter of Pht@PVP MC with uniform size distribution. The spherical Pht@PVP MC maintained its size and polydispersity index in a biological buffer for 2 weeks. Pht@PVP MC exhibited enhanced antibacterial activity compared to bare Pht. The growth of Staphylococcus aureus was effectively inhibited by Pht@PVP MC treatment. Furthermore, biocompatible Pht@PVP MC exhibited dose-dependent antioxidant and anti-inflammatory activities in vitro. Overall, Pht@PVP MC is an effective alternative to synthetic antibacterial, antioxidant, and anti-inflammatory chemicals.

Abstract Circadian clocks generate rhythms of arousal, but the underlying molecular and cellular mechanisms remain unclear. In Drosophila, the clock output molecule WIDE AWAKE (WAKE) labels rhythmic neural networks and cyclically regulates sleep and arousal. Here, we show, in a male mouse model, that mWAKE/ANKFN1 labels a subpopulation of dorsomedial hypothalamus (DMH) neurons involved in rhythmic arousal and acts in the DMH to reduce arousal at night. In vivo Ca2+ imaging reveals elevated DMHmWAKE activity during wakefulness and rapid eye movement (REM) sleep, while patch-clamp recordings show that DMHmWAKE neurons fire more frequently at night. Chemogenetic manipulations demonstrate that DMHmWAKE neurons are necessary and sufficient for arousal. Single-cell profiling coupled with optogenetic activation experiments suggest that GABAergic DMHmWAKE neurons promote arousal. Surprisingly, our data suggest that mWAKE acts as a clock-dependent brake on arousal during the night, when mice are normally active. mWAKE levels peak at night under clock control, and loss of mWAKE leads to hyperarousal and greater DMHmWAKE neuronal excitability specifically at night. These results suggest that the clock does not solely promote arousal during an animal’s active period, but instead uses opposing processes to produce appropriate levels of arousal in a time-dependent manner.

Abstract Human ATP-binding cassette transporter subfamily B6 (ABCB6) is a mitochondrial ATP-driven pump that translocates porphyrins from the cytoplasm into mitochondria for heme biosynthesis. Within the transport pathway, a conserved aromatic residue W546 located in each monomer plays a pivotal role in stabilizing the occluded conformation via π-stacking interactions. Herein, we employed cryo-electron microscopy to investigate the structural consequences of a single W546A mutation in ABCB6, both in detergent micelles and nanodiscs. The results demonstrate that the W546A mutation alters the conformational dynamics of detergent-purified ABCB6, leading to entrapment of the transporter in an outward-facing transient state. However, in the nanodisc system, we observed a direct interaction between the transporter and a phospholipid molecule that compensates for the absence of the W546 residue, thereby facilitating the normal conformational transition of the transporter toward the occluded state following ATP hydrolysis. The findings also reveal that adoption of the outward-facing conformation causes charge repulsion between ABCB6 and the bound substrate, and rearrangement of key interacting residues at the substrate-binding site. Consequently, the affinity for the substrate is significantly reduced, facilitating its release from the transporter.

Background/Aims: There are limitations in treating ampullary adenomas with intraductal extension using conventional endoscopic modalities. Endoscopic intraductal radiofrequency ablation (ID-RFA) may be useful for treating intraductal (common bile duct [CBD] and/or pancreatic duct [PD]) extensions of ampullary adenomas, but long-term data are lacking. We thus evaluated the long-term outcomes of endoscopic ID-RFA for managing ampullary adenomas with intraductal extension. Methods: Prospectively collected endoscopic ID-RFA database at Asan Medical Center was reviewed to identify consecutive patients with ampullary adenoma who underwent ID-RFA for intraductal extension between January 2018 and August 2021. Technical success, short-term and long-term clinical success, and adverse events were evaluated. Results: A total of 29 patients (14 CBD, 1 PD, and 14 CBD and PD) were analyzed. All patients had undergone endoscopic snare papillectomy prior to ID-RFA. A median of one session of ID-RFA (range, 1 to 3) for residual or relapsed intraductal extension of ampullary adenoma were successfully performed (technical success=100%). Both biliary and pancreatic stenting were routinely performed after ID-RFA to prevent ductal stricture. After a median follow-up of 776 days (interquartile range, 470 to 984 days), the short-term and long-term clinical success rates were 93% and 76%, respectively. Seven patients experienced procedural adverse events and three patients developed ductal strictures. Conclusions: Endoscopic ID-RFA showed good long-term outcomes in treating residual or relapsed ampullary adenomas with intraductal extension. Repeated ID-RFA may be considered as an option for managing recurrence. Further studies are needed to standardize the procedure.

Summary: The endoplasmic reticulum (ER) consists of the nuclear envelope and a connected peripheral network of tubules and interspersed sheets. The structure of ER tubules is generated and maintained by various proteins, including reticulons, DP1/Yop1p, atlastins, and lunapark. Reticulons and DP1/Yop1p stabilize the high membrane curvature of ER tubules, and atlastins mediate homotypic membrane fusion between ER tubules; however, the exact role of lunapark remains poorly characterized. Here, using isolated yeast ER microsomes and reconstituted proteoliposomes, we directly examined the function of the yeast lunapark Lnp1p for yeast atlastin Sey1p-mediated ER fusion and found that Lnp1p inhibits Sey1p-driven membrane fusion. Furthermore, by using a newly developed assay for monitoring trans-Sey1p complex assembly, a prerequisite for ER fusion, we found that assembly of trans-Sey1p complexes was increased by the deletion of LNP1 and decreased by the overexpression of Lnp1p, indicating that Lnp1p inhibits Sey1p-mediated fusion by interfering with assembly of trans-Sey1p complexes.

Abstract Crystal morphology of metal oxides in engineered metal-biochar composites governs the removal of phosphorus (P) from aqueous solutions. Up to our best knowledge, preparation of bio-assembled MgO-coated biochar and its application for the removal of P from solutions and kitchen waste fermentation liquids have not yet been studied. Therefore, in this study, a needle-like MgO particle coated tea waste biochar composite (MTC) was prepared through a novel biological assembly and template elimination process. The produced MTC was used as an adsorbent for removing P from a synthetic solution and real kitchen waste fermentation liquid. The maximum P sorption capacities of the MTC, deduced from the Langmuir model, were 58.80 mg g−1 from the solution at pH 7 and 192.8 mg g−1 from the fermentation liquid at pH 9. The increase of ionic strength (0–0.1 mol L−1 NaNO3) reduced P removal efficiency from 98.53% to 93.01% in the synthetic solution but had no significant impact on P removal from the fermentation liquid. Precipitation of MgHPO4 and Mg(H2PO4)2 (76.5%), ligand exchange (18.0%), and electrostatic attraction (5.5%) were the potential mechanisms for P sorption from the synthetic solution, while struvite formation (57.6%) and ligand exchange (42.2%) governed the sorption of P from the kitchen waste fermentation liquid. Compared to previously reported MgO-biochar composites, MTC had a lower P sorption capacity in phosphate solution but a higher P sorption capacity in fermentation liquid. Therefore, the studied MTC could be used as an effective candidate for the removal of P from aqueous environments, and especially from the fermentation liquids. In the future, it will be necessary to systematically compare the performance of metal-biochar composites with different metal oxide crystal morphology for P removal from different types of wastewater. Graphical Abstract

Abstract It is debatable which needle has clear superiority of diagnostic performance in endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB) of solid pancreatic masses. This study aimed to compare the performance of three needles and determine the variables that affect diagnostic accuracy. From March 2014 to May 2020, 746 patients with solid pancreatic masses who underwent EUS-FNB using three types of needles (Franseen needle, Menghini-tip needle, and Reverse-bevel needle) were retrospectively reviewed. Multivariate analysis using a logistic regression model was used to identify factors related to diagnostic accuracy. There were significant differences between the groups regarding the procurement rate of the histologic and optimal quality cores (Franseen vs. Menghini-tip vs. Reverse-bevel: 98.0% [192/196] vs. 85.8% [97/113] vs. 91.9% [331/360], P

Background: In-stent restenosis caused by tissue hyperplasia and tumor growth through the wire meshes of an implanted self-expandable metallic stent (SEMS) remains an unresolved obstacle. This study aimed to investigate the safety and efficacy of SEMS-mediated radiofrequency ablation (RFA) for treating stent-induced tissue hyperplasia in a rat gastric outlet obstruction model.Methods: The ablation zone was investigated using extracted porcine liver according to the ablation time. The optimal RFA parameters were evaluated in the dissected rat gastric outlet. We allocated 40 male rats to four groups of 10 rats as follows: group A, SEMS placement only; group B, SEMS-mediated RFA at 4 weeks; group C, SEMS-mediated RFA at 4 weeks and housed until 8 weeks; and group D, SEMS-mediated RFA at 4 and 8 weeks. Endoscopy and fluoroscopy for in vivo imaging and histological and immunohistochemical analysis were performed to compare experimental groups.Results: Stent placement and SEMS-mediated RFA with an optimized RFA parameter were technically successful in all groups. Granulation tissue formation-related variables were significantly higher in group A than in groups B–D (all p < 0.05). Endoscopic and histological findings confirmed that the degrees of stent-induced tissue hyperplasia in group D were significantly lower than in groups B and C (all p < 0.05). Hsp70 and TUNEL expressions were significantly higher in groups B–D than in group A (all p < 0.001).Conclusion: The implanted SEMS-mediated RFA successfully managed stent-induced tissue hyperplasia, and repeated or periodic RFA seems to be more effective in treating in-stent restenosis in a rat gastric outlet obstruction model.

The occurrence of antibiotics in agricultural soils has raised concerns due to their potential risks to ecosystems and human health. However, a comprehensive understanding of antibiotic accumulation, distribution, and potential risks to terrestrial ecosystems on a global scale is still limited. Therefore, in this study, we evaluated the accumulation of antibiotics and their potential risks to soil microorganisms and plants, and highlighted the driving factors of antibiotic accumulation in agricultural soils based on 134 peer-reviewed studies (between 2000 and 2022). The results indicated that 56 types of antibiotics were detected at least once in agricultural soils with concentrations ranging from undetectable to over 7000 µg/kg. Doxycycline, tylosin, sulfamethoxazole, and enrofloxacin, belonging to the tetracyclines, macrolides, sulfonamides, and fluoroquinolones, respectively, were the most accumulated antibiotics in agricultural soil. The accumulation of TCs, SAs, and FQs was found to pose greater risks to soil microorganisms (average at 29.3%, 15.4%, and 21.8%) and plants (42.4%, 26.0%, and 38.7%) than other antibiotics. East China was identified as a hot spot for antibiotic contamination due to high levels of antibiotic concentration and ecological risk to soil microorganisms and plants. Antibiotic accumulation was found to be higher in vegetable fields (245.5 µg/kg) and orchards (212.4 µg/kg) compared to croplands (137.2 µg/kg). Furthermore, direct land application of manure resulted in a greater accumulation of TCs, SAs, and FQs accumulation in soils than compost fertilization. The level of antibiotics decreased with increasing soil pH and organic matter content, attributed to decreasing adsorption and enhancing degradation of antibiotics. In conclusion, this study highlights the need for further research on the impacts of antibiotics on soil ecological function in agricultural fields and their interaction mechanisms. Additionally, a whole-chain approach, consisting of antibiotic consumption reduction, manure management strategies, and remediation technology for soil contaminated with antibiotics, is needed to eliminate the potential environmental risks of antibiotics for sustainable and green agriculture.

Abstract Endoluminal radiofrequency (RF) ablation has been widely used as a safe and effective treatment for Barrett’s esophagus. However, inadequate RF ablation may occur due to insufficient contact between the electrode and target tissues. Herein, a stent-based monopolar RF electrode (SE) was developed to evenly deliver RF energy to the inner wall of the rat esophagus. The optimal RF parameters were evaluated in the exposed rat esophagus. The temperature in the rat esophagus reached 70 ℃ in 89 s at 30 W, 59 s at 40 W, and 34 s at 50 W. The technical feasibility and efficacy of RF ablation using SE were evaluated based on changes in histological transformation and immunohistochemical parameters of tissues compared at immediately, 1 and 2 weeks after the procedure. The degrees of inflammatory cell infiltration, fibrotic changes, TUNEL, and HSP70 in the RF-ablated rat esophagus were significantly higher than compared with sham control (all p

Abstract In recent years, East Africa has been suffering from severe droughts. The availability of water is crucial to socioeconomic development and ecosystem services in the region. In order to address the pressing issue of water scarcity in the Wag Himra zone, a study will identify viable rainwater harvesting (RWH) sites. Geographical Information System with a multi-criteria evaluation system was used to identify suitable RWH sites based on land use and cover, soil texture, runoff depth, slope, drainage density, and considering road and town constraints. The runoff depth was estimated using the soil conservation service curve number model, and the land use/cover image classification was undertaken using ArcGIS. By using weighted overlay analysis, sites that are potentially suitable for RWH were identified. Based on the hydrological and socioeconomic characteristics of the study area and available literature, the weight of the criteria was determined using the Analytical Hierarchical Process. The findings of the study indicate that only 0.02% of the study area is considered highly suitable, 2.59, 12.26, 61.76, and 21.1% are rated as moderately suitable, marginally suitable, less suitable, and not suitable for RWH, respectively, and 2.29% is labeled a constraint for RWH. It is possible to harvest and store rainwater in the study area to meet increasing water demand. These findings aim to assist decision-makers, planners, and managers to find sites, invest in water resources, and use RWH as an alternative water source.

Abstract Background Although acute hepatitis E is not fatal in healthy individuals, it is unclear whether hepatitis E superinfection increases the mortality in patients with pre-existing liver disease. Thus, we investigated the prognosis of patients with acute hepatitis E according to their cirrhosis diagnosis, and the prognosis according to the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis and chronic liver disease (CLD). Methods This study included 74 consecutive patients who were diagnosed with acute viral hepatitis E between January 2007 and December 2019. Of them, 39 patients without CLD, 13 patients with non-cirrhotic CLD, and 22 patients with cirrhotic CLD were analyzed. Results Among the 74 patients with HEV infection, 7 (9.5%) died within 180 days: 5 with underlying cirrhosis (71.4%) and 2 without cirrhosis (28.6%). The 180-day mortality was significant higher for patients with cirrhosis than for patients without cirrhosis (22.7% vs. 3.8%, P = 0.013). The age- and sex-adjusted proportional-hazard model revealed an approximately eightfold increase in the 180-day mortality risk in patients with cirrhosis compared to patients without cirrhosis. In addition, development of hepatitis E virus-related ACLF due to acute liver function deterioration in patients with pre-existing CLD or cirrhosis worsened the 180-day mortality rate. Conclusions Our findings suggest that the acute hepatitis E mortality rate was low in healthy individuals but higher in patients with cirrhosis, and especially high in those with ACLF.

Background/Aims: The endoscopic step-up approach is accepted as the preferred treatment for complicated or symptomatic walled-off necrosis (WON). Direct endoscopic necrosectomy (DEN) is an effective therapeutic option, but few reports describe long-term follow-up in this patient population. Thus, we aim to assess the long-term outcomes of DEN following severe necrotizing pancreatitis. Methods: The data of all acute pancreatitis patients who underwent DEN following endoscopic transmural drainage from six referral centers between 2007 and 2017 were retrospectively collected. Results: Sixty patients (76.7% male, mean age 48.3 years) underwent a median of 4 sessions of DEN starting at a median of 45.5 days after the onset of acute pancreatitis. Clinical success was achieved in 51 patients (85%), with a 35% complication rate and a 5% mortality rate. Using multivariate analysis, the risk factor associated with DEN failure or major DEN complications requiring intervention or surgery was an identified bacterial/fungal WON infection (odds ratio, 19.3; 95% confidence interval, 1.5 to 261.7). During the median follow-up period of 27 months, complicated WON recurrence was observed in 5.3% of patients, and long-term complications occurred in 24.6% of patients (four exocrine insufficiency, nine newly developed diabetes mellitus, one recurrent small bowel obstruction, one chylous ascites). Conclusions: Considering that long-term complications are similar to those observed after pancreatectomy, DEN should be performed meticulously while minimizing damage to the viable pancreatic parenchyma with adequate antibiotic escalation.

Background/Aims The effect of hyperammonemia on the mortality in patients with liver cirrhosis is well documented. However, little is known about the impact of hyperammonemia on mortality among intensive care unit patients without hepatic disease. We aimed to investigate factors associated with non-hepatic hyperammonemia among intensive care unit patients and to evaluate the factors related to the 7- and 90-day mortality. Methods Between February 2016 and February 2020, 948 patients without hepatic disease who had 972 episodes of admission to the intensive care unit were retrospectively enrolled and classified as hyperammonemia grades 0 (≤ 80 μg/dL; 585 [60.2%]), 1 (≤ 160 μg/dL; 291 [29.9%]), 2 (≤ 240 μg/dL; 55 [5.7%]), and 3 (> 240 μg/dL; 41 [4.2%]). Factors associated with hyperammonemia and the 7- and 90-day mortality were evaluated by multivariate logistic regression analysis and Cox regression analysis, respectively. Kaplan-Meier survival curves for the 7- and 90-day mortality were constructed. Results The independent risk factors for hyperammonemia were male sex (odds ratio, 1.517), age (0.984/year), acute brain failure (2.467), acute kidney injury (1.437), prothrombin time-international normalized ratio (2.272/unit), and albumin (0.694/g/dL). The 90-day mortality rate in the entire cohort was 24.3% and gradually increased with increasing hyperammonemia grade at admission (17.9%, 28.2%, 43.6%, and 61.0% in patients with grades 0, 1, 2, and 3, respectively). Additionally, non-hepatic hyperammonemia was an independent predictor of the 90-day mortality in intensive care unit patients. Conclusions Non-hepatic hyperammonemia is common (39.8%) and associated with the 90-day mortality among intensive care unit patients.

Background: Irreversible electroporation (IRE) has been investigated in the alimentary tract; however, the lack of dedicated electrodes and insufficient tissue responses made its application limited. The aim of this study was to investigate the efficacy and safety of image-guided stent-directed IRE in the rat esophagus.Methods: The bipolar self-expandable electrode (SE) was developed using the braiding technique. A finite element analysis was performed to validate optimal electrical field strength for the rat esophagus. A total of 40 out of 50 rats received stent-directed IRE and were sacrificed at 10 h, 3 days, 7 days, and 28 days of 10 each. The remaining ten rats underwent a sham procedure. The outcomes of stent-directed IRE were assessed by esophagography and histological responses.Results: Stent-directed IRE was technically successful in all rats with mild muscle contraction. The heart rate dropped immediately and gradually recovered at 180 s. TUNEL and caspase-3 with submucosal thickness significantly increased at 10 h and Day 3 compared with those of the sham control (all p < 0.001). The thickness of epithelial layers with collagen deposition significantly decreased at 10 h and Day 3 (all p < 0.001), however, increased at Day 7 compared with that of the sham control (all p < 0.05). The Ki67-positive deposition significantly increased at Day 3 and 7 compared with that of the sham control (all p < 0.001). All variables were similar to those of the sham control at Day 28.Conclusion: Image-guided stent-directed IRE was effective and safe in the rat esophagus. It seems to have effectively and evenly induced cell death and gradually recovered with cellular regeneration.

Abstract Background The effect of acute kidney injury (AKI) on patients with acute variceal bleeding (AVB) using the recently proposed International Club of Ascites (ICA) criteria is unclear. This study aimed to evaluate the incidence of AKI using the ICA criteria and factors associated with the outcomes in cirrhotic patients with AVB. Methods This retrospective cohort study included data of cirrhotic patients with AVB from two centers in Korea. The association of the ICA criteria for AKI with 6-week mortality was analyzed through univariate and multivariate analyses using the Cox proportional hazard model. Results In total, there were 546 episodes of AVB in 390 patients, of which 425 and 121 episodes were due to esophageal and gastric variceal bleeding, respectively. Moreover, 153 patients fulfilled the ICA criteria for AKI, and 64, 30, 39, and 20 patients were diagnosed with stages 1a, 1b, 2, and 3, respectively. Conversely, 97 patients developed AKI within 42 days as per the conventional criteria. The 6-week mortality rate was significantly higher in patients with ICA-AKI than in patients without ICA-AKI; the occurrence of ICA-AKI was an independent factor for predicting the 6-week mortality. Conclusion The ICA criteria could help diagnose renal dysfunction earlier, and presence of AKI is a predictor of mortality in patients with cirrhosis and AVB.

Background: Adjuvant chemotherapy is the standard treatment after curative-intent surgery for pancreatic ductal adenocarcinoma (PDAC). The phase-3 ESPAC-4 trial demonstrated significantly improved overall survival (OS) with Gemcitabine plus capecitabine (GemCap) over Gemcitabine (Gem) in Europe. We conducted a retrospective efficacy and safety evaluation of GemCap versus Gem in an Asian population. Methods: This retrospective analysis included 292 patients with PDAC who received adjuvant Gem or GemCap after curative resection between January 2017 and December 2020 at Asan Medical Center, Seoul, Korea. Results: Adjuvant Gem and GemCap were administered to 161 (55.1%) and 131 (44.8%) patients, respectively. The Gem group had significantly older patients (median 66 versus 63 years, p = 0.001); otherwise, the groups had similar baseline characteristics. With median follow-up durations of 39.4 [95% confidence interval (CI), 36.9–45.0] and 39.4 (95% CI, 34.7–41.6) months in the Gem and GemCap groups, the median OS was 36.8 (95% CI, 29.7–43.5) and 46.1 (95% CI, 31.5–not reached) months in the Gem and GemCap groups, respectively [unadjusted hazard ratio (HR) = 0.7; 95% CI, 0.5–1.0; p = 0.07). The median recurrence-free survival was 14.3 (95% CI, 12.9–17.7) and 17.0 (95% CI, 13.3–28.2) months, respectively ( p = 0.5). Hand-foot skin reactions (any grade, 15.3% versus 0.6%; p median) were significantly associated with worse OS. Conclusions: Adjuvant GemCap showed the consistent clinical outcomes with the ESPAC-4 trial. As mFOLFIRINOX is the new standard treatment for medically fit patients with resected PDAC, further evaluation of optimal adjuvant chemotherapy in daily practice is warranted.

Abstract Background Acute kidney injury (AKI) is expected to occur commonly in patients with chronic hepatitis C. In addition, AKI may affect the survival of patients with chronic hepatitis C. However, few studies are available on this topic. We aimed to evaluate the incidence of AKI in patients with chronic hepatitis C and investigate the factors related to overall mortality. Methods Between January 2005 and December 2018, 1252 patients with chronic hepatitis C virus (HCV) infection, defined as persistent HCV RNA for at least 6 months, were retrospectively enrolled at two centers. Of them, 1008, 123, and 121 patients had chronic hepatitis (CH), compensated cirrhosis (Com-LC), and decompensated cirrhosis (Decom-LC) or hepatocellular carcinoma (HCC) at entry, respectively. Factors associated with AKI and overall mortality were evaluated using the Cox proportional regression model. The Kaplan-Meier survival curves for the development of AKI and overall mortality were generated. Results Over a mean follow-up period of 5.2 years, 285 patients developed AKI, with an incidence rate of 4.35 per 100 person-years. The incidence of AKI increased gradually with progression of chronic hepatitis C: CH (3.32 per 100 person-years), Com-LC (5.86 per 100 person-years), and Decom-LC or HCC (17.28 per 100 person-years). The patients without AKI showed better survival rates at 14 years than the patients with AKI (94.2% vs. 26.3%, P

Background/Aims: Interventional endoscopists may utilize contrast-enhanced harmonic endoscopic ultrasound (CEHEUS) for image guidance during radiofrequency ablation (RFA) because of its capability to delineate real-time tumor perfusion dynamics. The purpose of this study was to assess the utility of CEH-EUS for the guidance and monitoring of endoscopic RFA. Methods: Nineteen consecutive patients with solid abdominal tumors who underwent CEH-EUS and endoscopic RFA were included. The extent of the ablation was assessed by CEH-EUS at 5 to 7 days after RFA. Additional RFAs were performed under CEH-EUS guidance. Results: The diagnoses were as follows: nonfunctioning neuroendocrine tumor (n=13), solid pseudopapillary neoplasm (SPN) (n=2), insulinoma (n=1), left adrenal adenoma (n=2), and left adrenal oligometastasis (n=1). Pre-CEH-EUS findings revealed that 17 cases showed hyperenhanced patterns and two cases of SPN showed isoenhanced patterns. CEH-EUS-assisted RFA was technically feasible in all 19 patients. After the first RFA session, seven patients of the treated tumors showed the disappearance of intratumoral enhancement on CEH-EUS, whereas 12 showed residual contrast enhancement. Twelve patients with incomplete ablation were further treated with additional RFA under real-time CEH-EUS guidance. Radiologic complete response was observed in 13 patients (68.4%). Among the 35 ablation procedures, the only adverse events were two episodes of pancreatitis (5.7%; 1 moderate and 1 mild). During the median follow-up of 28 months, the local recurrence rate was 7.7%. Conclusions: The application of CEH-EUS for RFA could be helpful in assessing early treatment response after ablation and targeting residual viable tumors during additional ablation sessions.

Abstract Wettability control of carbonates is a central concept for enhanced petroleum recovery, but a mechanistic understanding of the associated molecular-scale chemical processes remains unclear. We directly probe the interface of calcium carbonate (calcite) with natural petroleum oil, synthetic petroleum analogues, and aqueous brines to understand the molecular scale behavior at this interface. The calcite–petroleum interface structure is similar whether or not calcite was previously exposed to an aqueous brine, and is characterized by an adsorbed interfacial layer, significant structural changes within the calcite surface, and increased surface roughness. No evidence for an often-assumed thin-brine wetting layer at the calcite–petroleum interface is observed. These features differ from those observed at the calcite–brine interface, and for parallel measurements using model synthetic petroleum mixtures (consisting of representative components, including dodecane, toluene, and asphaltene). Changes to the interface after petroleum displacement by aqueous brines are also discussed.

Background/Aims This study examined the risk factors associated with mortality in cirrhotic patients hospitalized with variceal bleeding, and evaluated the effects of acute-on-chronic liver failure (ACLF) on the prognosis of these patients. Methods This study was retrospectively conducted on patients registered in the Korean acute-on-chronic liver failure study cohort, and on 474 consecutive cirrhotic patients hospitalized with variceal bleeding from January 2013 to December 2013 at 21 university hospitals. ACLF was defined as described by the European Association for the Study of Liver-Chronic Liver Failure Consortium. Results Among a total of 474 patients, 61 patients were diagnosed with ACLF. The cumulative overall survival (OS) rate was lower in the patients with ACLF than in those without (P

Background/Aims: The natural history of spontaneous decrease in the size of pancreatic cystic lesions (PCLs) without high-risk stigmata is under investigation. This study aimed to investigate the timing of spontaneous decrease in the size of PCLs without high-risk stigmata and to identify the characteristics associated with their complete resolution. Methods: From 2000 to 2016, patients with spontaneous decreases in PCL size on computed tomography (CT) and/or magnetic resonance imaging (MRI) who had at least 1 year of follow-up were evaluated retrospectively. Results: A total of 78 patients underwent follow-up for an average of 55.7 months. Most patients were asymptomatic, and 35 (37.2%) showed complete resolution. The initial mean PCL size was 1.6±0.9 cm (range, 0.5 to 5.6 cm). The average time to initial decrease in size and complete resolution of PCLs were 32.1 and 41.5 months, respectively. Compared with PCLs that completely resolved, presence of underlying malignancy was associated with partial resolution of PCLs in multivariable analysis (hazard ratio, 0.51; 95% confidence interval, 0.32 to 0.81; p=0.005). Endoscopic ultrasound (EUS) identified detailed findings, especially the presence of septum (p

To improve the sulfur tolerance of CeO2-supported Pt catalysts for water gas shift (WGS) using waste-derived synthesis gas, we investigated the effect of synthesis methods on the physicochemical properties of the catalysts. The Pt catalysts using CeO2 as a support were synthesized in various pathways (i.e., incipient wetness impregnation, sol-gel, hydrothermal, and co-precipitation methods). The prepared samples were then evaluated in the WGS reaction with 500 ppm H2S. Among the prepared catalysts, the Pt-based catalyst prepared by incipient wetness impregnation showed the highest catalytic activity and sulfur tolerance due to the standout factors such as a high oxygen-storage capacity and active metal dispersion. The active metal dispersion and oxygen-storage capacity of the catalyst showed a correlation with the catalytic performance and the sulfur tolerance.

BackgroundGallbladder cancer (GBC) has a poor prognosis. Although complete surgical resection is the only successful approach for improving survival, additional therapeutic modalities are required for recurrent or surgically unresectable GBCs.Materials and MethodsTo determine the expression status of HER2 and the mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, immunohistochemical staining of MMR proteins and HER2 was carried out in 216 surgically resected GBCs. HER2 labeling was scored by adopting a scoring system for gastric carcinomas. Tissues scoring 0 to 2+ were defined as HER2 negative, whereas those scoring 3+ were regarded as HER2-positive. In addition, silver in situ hybridization and microsatellite instability (MSI) analysis were conducted to confirm HER2 amplification and MSI, respectively.ResultsThree of 216 GBCs (1.3%) showed MMR protein deficiency. All three observed MSI cases exhibited dual loss of MSH2 and MSH6 protein expression. However, no cases showed loss of either MLH1 or PMS2 expression. No association was observed between MMR protein deficiency and other clinicopathological factors. HER2 amplification was noted in 30 (13.9%) GBCs and associated with Crohn-like lymphoid reaction (P = 0.023). No survival difference was observed based on HER2 overexpression or HER2 amplification status.ConclusionMMR protein deficiency and HER2 overexpression were observed in a small subset (1.3% and 13.9%, respectively) of GBCs without simultaneous occurrence of deficient MMR protein expression and HER2 overexpression. The presence of Crohn-like lymphoid reaction may help identify cases with HER2 amplification, by using hematoxylin-stained slides. Although the proportion of MMR protein-deficient- and HER2-overexpressing GBCs was small, applying immunotherapy to MMR protein-deficient GBCs and herceptin to HER2-overexpressing GBCs may provide alternative treatment options for patients with GBC.

Abstract Background There is currently no evidence that hepatitis C virus (HCV) genotype affects survival in patients with hepatocellular carcinoma (HCC). This study aimed to investigate whether the HCV genotype affected the survival rate of patients with HCV-related HCC. Methods We performed a retrospective cohort study using the data of patients with HCV-related HCC evaluated at two centers in Korea between January 2005 and December 2016. Propensity score matching between genotype 2 patients and non-genotype 2 patients was performed to reduce bias. Results A total of 180 patients were enrolled. Of these, 86, 78, and 16 had genotype 1, genotype 2, and genotype 3 HCV-related HCC, respectively. The median age was 66.0 years, and the median overall survival was 28.6 months. In the entire cohort, patients with genotype 2 had a longer median overall survival (31.7 months) than patients with genotype 1 (28.7 months; P = 0.004) or genotype 3 (15.0 months; P = 0.003). In the propensity score–matched cohort, genotype 2 patients also showed a better survival rate than non-genotype 2 patients (P = 0.007). Genotype 2 patients also had a longer median decompensation-free survival than non-genotype 2 patients (P = 0.001). However, there was no significant difference in recurrence-free survival between genotype 2 and non-genotype 2 patients who underwent curative treatment (P = 0.077). In multivariate Cox regression analysis, non-genotype 2 (hazard ratio, 2.19; 95% confidence interval, 1.29–3.71) remained an independent risk factor for death. Conclusion Among patients with HCV-related HCC, those with genotype 2 have better survival.

Small cell carcinomas are the most aggressive, highly malignant neuroendocrine tumors; among these, gastric small cell carcinoma (GSCC) is extremely rare. Here we report a case of a patient with primary GSCC, presenting as linitis plastic, who was diagnosed using endoscopic ultrasound (EUS)-guided biopsy. With undiagnosed linitis plastica, an 80-year-old woman was referred to our institution. Abdominal computed tomography revealed irregular wall thickening extending from the gastric body to the antrum. Endoscopy suspected to have Borrmann type IV advanced gastric cancer. EUS of the stomach showed diffuse submucosal thickening of the gastric wall, mainly the antrum. EUS-guided bite-on-bite biopsy confirmed the diagnosis of GSCC. In general, GSCC is difficult to diagnose and careful examination is necessary to determine the therapeutic strategy; however, EUS is particularly helpful in the differential diagnosis of a lesion presenting as linitis plastica.

Background/Aims Type 2 autoimmune pancreatitis (AIP) has been considered extremely rare in East Asia. This study aimed to clarify the prevalence, clinical characteristics and radiological findings of type 2 AIP highlighting patients presenting as acute pancreatitis in a single center. Methods : Type 2 AIP patients were classified according to International Consensus Diagnostic Criteria. Radiological findings were compared between type 2 AIP presenting as acute pancreatitis and gallstone pancreatitis. Results : Among 244 patients with AIP, 27 (11.1%) had type 2 AIP (definite, 15 [55.5%] and probable 12 [44.5%]). The median age of patients with type 2 AIP was 29 years (interquartile range, 20 to 39 years). Acute pancreatitis was the most common initial presentation (n=17, 63%) while obstructive jaundice was present in only one patient. Ulcerative colitis (UC) was associated with type 2 AIP in 44.4% (12/27) of patients. Radiological pancreatic imaging such as delayed enhancement of diffusely enlarged pancreas, homogeneous enhancement of focal enlargement/mass, absent/minimal peripancreatic fat infiltration or fluid collection, and multifocal main pancreatic duct narrowings were helpful for differentiating type 2 AIP from gallstone pancreatitis. During follow-up (median, 32.3 months), two patients (2/25, 8%) experienced relapse. Conclusion : s In South Korea, type 2 AIP is not as rare as previously thought. Overall, the clinical profile of type 2 AIP was similar to that of Western countries. Type 2 AIP should be considered in young UC patients with acute pancreatitis of uncertain etiology.

Food security is a high-priority issue for sustainable global development both quantitatively and qualitatively. In recent decades, adverse effects of unexpected contaminants on crop quality have threatened both food security and human health. Heavy metals and metalloids (e.g., Hg, As, Pb, Cd, and Cr) can disturb human metabolomics, contributing to morbidity and even mortality. Therefore, this review focuses on and describes heavy metal contamination in soil–food crop subsystems with respect to human health risks. It also explores the possible geographical pathways of heavy metals in such subsystems. In-depth discussion is further offered on physiological/molecular translocation mechanisms involved in the uptake of metallic contaminants inside food crops. Finally, management strategies are proposed to regain sustainability in soil–food subsystems. Keywords: Heavy metals, Health risks, Wastewater, Nanoparticles, Vegetables, Eco-remediation

Oxidation of magnetite has broad implications in geochemistry and environmental science, but its reaction mechanisms are not fully understood yet. Here the authors use Bragg coherent diffractive imaging to show oxidative dissolution of magnetite inducing a rich array of strain and defect structures.

In South Korea, a water supply enhancement project is being carried out to preemptively respond to drought and water loss by reducing pipeline leakages and supplying stable tap water through the maintenance of an aging water supply network. In order to reduce water leakage, a District Metered Area (DMA) was established to monitor and predict the minimum night flow based on flow data collected from IoT sensors. In this study, a model based on Multi-Layer Perceptron (MLP) and Long Short-Term Memory (LSTM) was constructed to predict the MNF (minimum night flow) of County Y. The prediction of MNF results was compared with the MLP networks and the LSTM model. The outcome showed that the LSTM-MNF model proposed in this study performed better than the MLP-MNF model. Therefore, the research methods of this study can contribute to technical support for leakage reductions by preemptively responding to the expected increase in leakage through the prediction of the minimum flow at night.

Abstract Background Abdominal tuberculosis (TB) is an uncommon form of infection with Mycobacterium tuberculosis in Korea. In this study, we aimed to highlight the clinical features, diagnostic methods, and outcomes of abdominal TB over 12 years in Southeastern Korea. Methods A total of 139 patients diagnosed as having abdominal TB who received anti-TB medication from January 2005 to June 2016 were reviewed. Among them, 69 patients (49.6%) had luminal TB, 28 (20.1%) had peritoneal TB, 7 (5.0%) had nodal TB, 23 (16.5%) had visceral TB, and 12 (8.6%) had mixed TB. Results The most frequent symptoms were abdominal pain (34.5%) and abdominal distension (21.0%). Diagnosis of abdominal TB was confirmed using microbiologic and/or histologic methods in 76 patients (confirmed diagnosis), while the remaining 63 patients were diagnosed based on clinical presentation and radiologic imaging (clinical diagnosis). According to diagnostic method, frequency of clinical diagnosis was highest in patients with luminal (50.7%) or peritoneal (64.3%) TB, while frequency of microscopic diagnosis was highest in patients with visceral TB (68.2%), and frequency of histologic diagnosis was highest in patients with nodal TB (85.2%). Interestingly, most patients, except those with nodal TB, showed a good response to anti-TB agents, with 84.2% showing a complete response. The mortality rate was only 1.4% in the present study. Conclusions Most patients responded very well to anti-TB therapy, and surgery was required in only a minority of cases of suspected abdominal TB.

Endocrine state is an important determinant of learning and memory in animals. In Drosophila, rejection of male courtship overtures by mated females leads to an aversive response manifested as courtship memory. Here we report that ecdysis triggering hormone (ETH) is an obligatory enabler of long-term courtship memory (LTM). ETH deficiency suppresses LTM, whereas augmented ETH release reduces the minimum training period required for LTM induction. ETH receptor knockdown either in the mushroom body (MB) γ lobe or in octopaminergic dorsal-anterior-lateral (DAL) neurons impairs memory performance, indicating its direct action in these brain areas. Consistent with these findings, brain exposure to ETH mobilizes calcium in MB γ lobe neuropils and DAL neurons. ETH receptor (ETHR) knockdown in the corpus allatum (CA) to create juvenile hormone (JH) deficiency also suppresses LTM, as does knockdown of the JH receptor Met in the MB γ lobe, indicating a convergence of ETH and JH signaling in this region of the brain. Our findings identify endocrine-enabled neural circuit components in the brain that are critical for persistent behavioral changes resulting from aversive social experience.

IntroductionFor unresectable hilar obstruction, restoring and maintaining biliary ductal patency are crucial for improved survival and quality of life. The endoscopic placement of stents is now a mainstay of its treatment, and bilateral stenting is effective for biliary decompression. This study aimed to determine the clinical outcomes of bilateral metal stent placement using large cell-type stents and the clinical predictors of stent dysfunction in patients with malignant hilar obstruction.MethodsWe performed a retrospective analysis of patients who underwent bilateral metal stent placement using two large cell-type stents at two academic teaching hospitals between September 2017 and February 2019. The primary outcome was stent dysfunction. Secondary outcomes included predictors related to stent dysfunction and overall survival.ResultsThe study included 87 patients who underwent bilateral metal stent placement for malignant hilar obstruction. Technical success and clinical success were achieved in 80 patients (92.0%) and 83 patients (95.4%), respectively. During the follow-up period (median: 201, range: 18-671 days), stent dysfunction occurred in 42 patients (48.3%), and the median stent patency was 199 days (95% confidence interval [CI]: 181-262). In univariate analysis, age, cholangitis before stent insertion, and subsequent chemotherapy were found to be associated with the cumulative risk of stent dysfunction. In multivariate analysis, cholangitis before stent insertion (hazards ratio [HR]: 2.26, 95% CI: 1.216-4.209, P = 0.010) and subsequent chemotherapy (HR: 0.250, 95% CI: 0.130-0.482, PConclusionThe bilateral placement of large cell-type stents for malignant hilar obstruction was effective with high technical and clinical success rates and acceptable patency. Cholangitis before stent insertion was associated with shorter patency, and subsequent chemotherapy was associated with longer stent patency.

Intraductal radiofrequency (RF) ablation combined with placement of a self-expandable metal stent (SEMS) for malignant biliary obstruction has risks such as stent- and heat-induced biliary sludge and restenosis. Here, we investigated the efficacy of a silver nanoparticles (AgNPs)-coated SEMS to inhibit tissue hyperplasia and bacterial growth caused by RF ablation with stent placement in the rabbit bile duct. The release behavior and antibacterial effects of AgNPs-coated SEMSs were evaluated. Then, SEMSs were successfully placed in all rabbits immediately after RF ablation. Ag ions were rapidly released at the beginning and then showed a gradual release behavior. The AgNPs-coated SEMS significantly inhibited bacterial activity compared to the uncoated SEMS (p < 0.05). Cholangiography and histological examination confirmed that the level of tissue hyperplasia was significantly lower in the AgNPs group than in the control group (all p < 0.05). Immunohistochemistry analyses revealed that TUNEL-, HSP 70-, and α-SMA-positive areas were significantly lower in the AgNPs group than in the control group (all p < 0.05). Intraductal RF ablation combined with nanofunctionalized stent placement represents a promising new approach for suppressing thermal damage as well as stent-induced tissue hyperplasia and bacterial growth.

Background: Despite the scarcity of data based on randomized trials, FOLFIRINOX is widely used in the management of borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). We investigated the clinical outcomes of neoadjuvant FOLFIRINOX in patients with BRPC and LAPC. Methods: This single-center retrospective analysis included a total of 199 consecutive patients with BRPC or LAPC who received conventional or modified FOLFIRINOX between February 2013 and January 2017. An independent radiologist reviewed all baseline computed tomography or magnetic resonance imaging scans were reviewed for vascular invasion status. Results: With median follow-up duration of 40.3 months [95% confidence interval (CI), 36.7–43.8] in surviving patients, median progression-free survival (PFS) and overall survival (OS) were 10.6 (95% CI, 9.5–11.7) and 18.1 (95% CI, 16.0–20.3) months, respectively. The 1-year PFS rate was 66.0% (95% CI, 65.3–66.7%), and the 2-year OS rate was 37.2% (95% CI, 36.5–37.9%). PFS and OS did not differ between BRPC and LAPC groups [median PFS, 11.1 months (95% CI, 8.8–13.5) versus 10.1 months (95% CI, 8.4–11.8), p = 0.47; median OS, 18.4 months (95% CI, 16.1–20.8) versus 17.1 months (95% CI, 13.2–20.9), p = 0.50]. Curative-intent conversion surgery (R0/R1) was performed in 63 patients (31.7%). C•A 19-9 response, objective tumor response to FOLFIRINOX, and conversion surgery were independent prognostic factors for OS. Conclusion: FOLFIRINOX was effective for management of BRPC and LAPC. Given the potential for cure, a significant proportion of patients can undergo conversion curative-intent surgery following FOLFIRINOX.

With rapid increases in population and urbanization, uncontrolled municipal solid waste (MSW) is a threat to public health and environmental safety. In this study, we explore its generation, treatment, and characteristics of physical/chemical composition and assess the potential of MSW as a renewable energy source in Lahore, the second largest city in Pakistan. Based on the average generation rate of MSW (i.e., 0.65 kg/capita/day), the daily production of MSW in this city would reach 7150 tons/day. However, its disposal in a safely engineered way has been restricted due to the lack of: (a) pre-planning, (b) infrastructure, (c) political will, and (d) public awareness. Various samples of MSW considering socio-economic structure were collected. The physical components of MSW in Lahore were found to be in the descending order of biodegradable, nylon plastic bags, textile, diaper, and paper. The inductively coupled plasma optical emission spectroscopy (ICP-OES) technique was used to determine the heavy metal content and leachability of the MSW components to check for the environmental contamination risk. The proximate and ultimate analysis of this MSW was also carried out along with its heating values. The average high heating value of MSW was measured as 14,490 kJ kg−1. Energy recovery potential of 48 MW was assessed further from 2000 tons of MSW/day. The results of this study should be helpful for policy makers to establish a MSW management strategy for the potential renewable energy alternative. Keywords: Incineration, Landfills, Municipal solid waste, Renewable energy, Waste to energy

Background/AimsDifferentially diagnosing focal-type autoimmune pancreatitis (f-AIP) and pancreatic cancer (PC) is challenging. Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) may provide information for differentiating pancreatic masses. In this study, we evaluated the usefulness of CEH-EUS in differentiating f-AIP from PC.Methods : Data were collected prospectively and analyzed on patients who underwent CEH-EUS between May 2014 and May 2015. Eighty consecutive patients were diagnosed with f-AIP or PC. PC and f-AIP were compared for enhancement intensity, contrast agent distribution, and internal vasculature.Results : The study group comprised 53 PC patients and 27 f-AIP patients (17 with type-1 AIP [15 definite and two probable], two with probable type-2 AIP, and eight with AIP, not otherwise specified). Hyper- to iso-enhancement in the arterial phase (f-AIP, 89% vs PC, 13%; p

This study investigated whether interwoven self-expandable metallic stent (I-SEMS) placement suppresses stent-induced tissue hyperplasia compared with conventional knitted self-expandable metallic stent (K-SEMS) placement in a rat esophageal model. Twelve rats were randomly assigned to the I-SEMS (n = 6) and K-SEMS (n = 6) groups. All rats were sacrificed 4 weeks after the stent placement. The degree of stent-induced tissue hyperplasia on esophagography and histologic examination was compared between the groups. Stent placement was technically successful in all rats. Esophagography revealed significantly greater mean luminal diameter of the stented esophagus in the I-SEMS group than in the K-SEMS group (p < 0.001). Histologic examination revealed a significantly lower percentage of tissue hyperplasia area and a significantly thinner submucosal fibrosis in the I-SEMS group than in the K-SEMS group (all p < 0.001). There were no significant differences in the thickness of the epithelial layers (p = 0.290) and degree of inflammatory cell infiltration (p = 0.506). Formation of stent-induced tissue hyperplasia was evident with both I-SEMS and K-SEMS. Placement of I-SEMSs with a small cell size and high flexibility seems to be effective in suppressing stent-induced tissue hyperplasia compared with placement of K-SEMSs in rat esophageal models.

Ion exchange at charged mineral-water interfaces is an important geochemical process, but a molecular-level understanding is still required. Here, the authors probe real-time variations of the interfacial ion exchange dynamics at the muscovite-water interface, providing a general picture of adsorbed ion coverage and speciation.

Background/Aims Little is known about the treatment or outcomes of hepatocellular carcinoma (HCC) complicated with bile duct invasion. Methods A total of 247 consecutive HCC patients with bile duct invasion at initial diagnosis were retrospectively included. Results The majority of patients had Barcelona Clinic Liver Cancer (BCLC) stage C HCC (66.8%). Portal vein tumor thrombosis was present in 166 (67.2%) patients. Median survival was 4.1 months. Various modalities of treatment were initially employed including surgical resection (10.9%), repeated transarterial chemoembolization (TACE) (42.5%), and conservative management (42.9%). Among the patients with obstructive jaundice (n=88), successful biliary drainage was associated with better overall survival rate. Among the patients with BCLC stage C, overall survival differed depending on the initial treatment for HCC; surgical resection, TACE, systemic chemotherapy, and conservative management showed overall survival rates of 11.5, 6.0 ,2.4, and 1.6 months, respectively. After adjusting for confounders, surgical resection and repeated TACE were significant prognostic factors for HCC patients with bile duct invasion (hazard ratios 0.47 and 0.39, Ps

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.

Background and study aims The aim of the current study was to review the outcomes of a large-scale international registry on endoscopic ultrasound-guided gallbladder drainage (EGBD) that encompasses different stent systems in patients who are at high-risk for cholecystectomy. Patients and methods This was a retrospective international multicenter registry on EGBD created by 13 institutions around the world. Consecutive patients who received EGBD for several indications were included. Outcomes include technical and clinical success, unplanned procedural events (UPE), adverse events (AEs), mortality, recurrent cholecystitis and learning curve of the procedure. Results Between June 2011 and November 2017, 379 patients were recruited to the study. Technical and clinical success were achieved in 95.3 % and 90.8 % of the patients, respectively. The 30-day AE rate was 15.3 % and 30-day mortality was 9.2 %. UPEs were significantly more common in patients with EGBD performed for conversion of cholecystostomy and symptomatic gallstones (P

PurposeStereotactic body radiation therapy (SBRT) is a promising treatment modality for locally advanced pancreatic cancer (LAPC). We evaluated the clinical outcomes of SBRT in patients with LAPC.Patients and methodsWe retrospectively analyzed the medical records of patients with LAPC who underwent SBRT at our institution between April 2011 and July 2016. Fiducial markers were implanted using endoscopic ultrasound guidance one week prior to 4-dimensional computed tomography (CT) simulation and daily cone beam CT was used for image guidance. Patients received volumetric modulated arc therapy or intensity modulated radiotherapy using respiratory gating technique. A median dose of 28 Gy (range, 24-36 Gy) was given over four consecutive fractions delivered within one week. Survival outcomes including freedom from local disease progression (FFLP), progression-free survival (PFS), and overall survival (OS) were analyzed. Acute and late toxicities related to SBRT were assessed.ResultsA total of 95 patients with LAPC were analyzed, 52 of which (54.7%) had pancreatic head cancers. Most (94.7%) had received gemcitabine-based chemotherapy. The 1-year FFLP rate was 80.1%. Median OS and PFS were 16.7 months and 10.2 months, respectively; the 1-year OS and PFS rates were 67.4% and 42.9%, respectively. Among 79 patients who experienced failure, the sites of first failures were isolated local progressions in 12 patients (15.2%), distant metastasis in 55 patients (69.6%), and both in 12 patients (15.2%). Seven patients (7.4%) were able to undergo surgical resection after SBRT and four had margin-negative resections. Three patients (3.2%) had grade 3 nausea/vomiting during SBRT, and late grade 3 toxicity was observed in another three patients.ConclusionsLAPC patients who received chemotherapy and SBRT had favorable FFLP and OS with minimal treatment-related toxicity. The most common pattern of failure was distant metastasis, which warrants further studies on the optimal scheme of chemotherapy and SBRT.