HDAC inhibitor SB939 potentiates TRAIL-induced apoptosis in colorectal cancer cells.

Colorectal cancer (CRC) displays noticeable resistance to chemotherapeutic drugs or innovative tumor cell apoptosis-inducing agents such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Thus, sensitizers are needed to enhance the effects of TRAIL-based cancer therapies. Elevated tumor cell death has been reported when various HDAC inhibitors are administered with TRAIL in various human cancers; however, SB939-TRAIL combined treatment has not been reported. In this study, we determined the ability of SB939 and TRAIL, as single agents or in combination, to inhibit the growth and survival of colorectal cancer cells. Our results demonstrated the effects of SB939 and TRAIL on cell viability, apoptosis, and morphological changes in HT-29 cells. SB939 treatment induces hyper-acetylation of histones and death receptors (DR) by activating MAPK proteins in a dose- and time-dependent manner. The ability of SB939 to sensitize HT-29 cells suggests that SB939 can induce essential changes in cell signaling pathways. Thus, the pan-HDAC inhibitor SB939 sensitizes TRAIL-induced apoptosis via up-regulation of DR5, and SB939-TRAIL combined treatment may target the MAPK pathways and serve as an effective therapeutic strategy against CRC.

Identification of Point Defects in Atomically Thin Transition-Metal Dichalcogenide Semiconductors as Active Dopants.

Selective doping in semiconductors is essential not only for monolithic integrated circuity fabrications but also for tailoring their properties including electronic, optical, and catalytic activities. Such active dopants are essentially point defects in the host lattice. In atomically thin two-dimensional (2D) transition-metal dichalcogenides (TMDCs), the roles of such point defects are particularly critical in addition to their large surface-to-volume ratio, because their bond dissociation energy is relatively weaker, compared to elemental semiconductors. In this Mini Review, we review recent advances in the identifications of diverse point defects in 2D TMDC semiconductors, as active dopants, toward the tunable doping processes, along with the doping methods and mechanisms in literature. In particular, we discuss key issues in identifying such dopants both at the atomic scales and the device scales with selective examples. Fundamental understanding of these point defects can hold promise for tunability doping of atomically thin 2D semiconductor platforms.

Consistency of Helicobacter pylori eradication rates of first-line concomitant and sequential therapies in Korea: A nationwide multicenter retrospective study for the last 10 years.

BACKGROUND: Eradication rate of standard triple therapy for H. pylori has declined to unacceptable level, and alternative regimens such as concomitant and sequential therapy have been introduced. We aimed to assess the consistency of eradication rates of concomitant and sequential therapies as for the first-line H. pylori eradication in Korea. METHODS: A nationwide multicenter retrospective study was conducted including 18 medical centers from January 2008 to December 2017. We included 3,800 adults who had test to confirm H. pylori eradication within 1 year after concomitant or sequential therapy. RESULTS: Concomitant and sequential therapy were prescribed for 2508 and 1292 patients, respectively. The overall eradication rate of concomitant therapy was significantly higher than that of sequential therapy (91.8% vs. 86.1%, p < .001). In time trend analysis, the eradication rates of concomitant therapy were 90.2%, 88.2%, 92.1%, 94.3%, 91.1%, and 93.4% for each year from 2012 to 2017 with an increasing trend (p = .0146), while those of ST showed no significant trend (p = .0873). Among 263 patients with second-line therapy, bismuth quadruple therapy showed significantly higher eradication rate than quinolone-based triple therapy (73.9% vs. 51.5% in ITT analysis, p = .001; 82.7% vs. 63.0% in PP analysis, p = .002). CONCLUSION: Concomitant therapy is the best regimen for the first-line H. pylori eradication showing consistently higher eradication rate with an increasing trend for the last 10 years in Korea. Bismuth quadruple therapy should be considered for second-line therapy after eradication failure using non-bismuth quadruple therapy.

Maximal diameter of liver abscess independently predicts prolonged hospitalization and poor prognosis in patients with pyogenic liver abscess.

BACKGROUND/AIMS: This study aimed to investigate the factors associated with prolonged hospital stay and in-hospital mortality in patients with pyogenic liver abscess. METHODS: We retrospectively reviewed data from patients with pyogenic liver abscess who were admitted between 2005 and 2018 at three tertiary hospitals in Jeonbuk province, South Korea. Prolonged hospital stay was defined as a duration of hospital admission of more than 21 days. RESULTS: A total of 648 patients (406 men and 242 women) diagnosed with pyogenic liver abscess were enrolled in the study. The mean maximal diameter of the liver abscess was 5.4 ± 2.6 cm, and 74.9% of the lesions were single. The three groups were divided according to the maximal diameter of the abscess. Laboratory parameters indicated a more severe inflammatory state and higher incidence of complications and extrahepatic manifestations with increasing abscess size. Rates of percutaneous catheter drainage (PCD) insertion, multiple PCD drainage, and salvage procedures as well as duration of drainage were also higher in the large liver abscess group. Of note, the duration of hospitalization and in-hospital mortality were significantly higher in the large hepatic abscess group. A multivariate analysis revealed that underlying diabetes mellitus, hypoalbuminemia, high baseline high-sensitivity C-reactive protein (hs-CRP) and procalcitonin levels, and large maximal abscess diameter were independent factors associated with prolonged hospital stay. Regarding in-hospital mortality, acute kidney injury at admission and maximal diameter of the abscess were independent factors associated with in-hospital mortality. CONCLUSIONS: A large maximal diameter of the liver abscess at admission indicated prolonged hospitalization and poor prognosis. More aggressive treatment strategies with careful monitoring are warranted in patients with large liver abscesses.

Epitaxial van der Waals Contacts between Transition-Metal Dichalcogenide Monolayer Polymorphs.

We have achieved heteroepitaxial stacking of a van der Waals ( vdW) monolayer metal, 1T'-WTe2, and a semiconductor, 2H-WSe2, in which a distinctively low contact barrier was established across a clean epitaxial vdW gap. Our epitaxial 1T'-WTe2 films were identified as a semimetal by low temperature transport and showed the robust breakdown current density of 5.0 × 107 A/cm2. In comparison with a series of planar metal contacts, our epitaxial vdW contact was identified to possess intrinsic Schottky barrier heights below 100 meV for both electron and hole injections, contributing to superior ambipolar field-effect transistor (FET) characteristics, i.e., higher FET mobilities and higher on-off current ratios at smaller threshold gate voltages. We discuss our observations around the critical roles of the epitaxial vdW heterointerfaces, such as incommensurate stacking sequences and absence of extrinsic interfacial defects that are inaccessible by other contact methods.

Electroluminescence from h-BN by using Al2O3/h-BN multiple heterostructure.

Two-dimensional (2-D) hexagonal boron nitride (h-BN) has attracted considerable attention for deep ultraviolet optoelectronics and visible single photon sources, however, realization of an electrically-driven light emitter remains challenging due to its wide bandgap nature. Here, we report electrically-driven visible light emission with a red-shift under increasing electric field from a few layer h-BN by employing a five-period Al2O3/h-BN multiple heterostructure and a graphene top electrode. Investigation of electrical properties reveals that the Al2O3 layers act as potential barriers confining injected carriers within the h-BN wells, while suppressing the electrostatic breakdown by trap-assisted tunneling, to increase the probability of radiative recombination. The result highlights a promising potential of such multiple heterostructure as a practical and efficient platform for electrically-driven light emitters based on wide bandgap two-dimensional materials.

Control over Electron-Phonon Interaction by Dirac Plasmon Engineering in the Bi2Se3 Topological Insulator.

Understanding the mutual interaction between electronic excitations and lattice vibrations is key for understanding electronic transport and optoelectronic phenomena. Dynamic manipulation of such interaction is elusive because it requires varying the material composition on the atomic level. In turn, recent studies on topological insulators (TIs) have revealed the coexistence of a strong phonon resonance and topologically protected Dirac plasmon, both in the terahertz (THz) frequency range. Here, using these intrinsic characteristics of TIs, we demonstrate a new methodology for controlling electron-phonon interaction by lithographically engineered Dirac surface plasmons in the Bi2Se3 TI. Through a series of time-domain and time-resolved ultrafast THz measurements, we show that, when the Dirac plasmon energy is less than the TI phonon energy, the electron-phonon coupling is trivial, exhibiting phonon broadening associated with Landau damping. In contrast, when the Dirac plasmon energy exceeds that of the phonon resonance, we observe suppressed electron-phonon interaction leading to unexpected phonon stiffening. Time-dependent analysis of the Dirac plasmon behavior, phonon broadening, and phonon stiffening reveals a transition between the distinct dynamics corresponding to the two regimes as the Dirac plasmon resonance moves across the TI phonon resonance, which demonstrates the capability of Dirac plasmon control. Our results suggest that the engineering of Dirac plasmons provides a new alternative for controlling the dynamic interaction between Dirac carriers and phonons.

Self-Formed Channel Devices Based on Vertically Grown 2D Materials with Large-Surface-Area and Their Potential for Chemical Sensor Applications.

2D layered materials with sensitive surfaces are promising materials for use in chemical sensing devices, owing to their extremely large surface-to-volume ratios. However, most chemical sensors based on 2D materials are used in the form of laterally defined active channels, in which the active area is limited to the actual device dimensions. Therefore, a novel approach for fabricating self-formed active-channel devices is proposed based on 2D semiconductor materials with very large surface areas, and their potential gas sensing ability is examined. First, the vertical growth phenomenon of SnS2 nanocrystals is investigated with large surface area via metal-assisted growth using prepatterned metal electrodes, and then self-formed active-channel devices are suggested without additional pattering through the selective synthesis of SnS2 nanosheets on prepatterned metal electrodes. The self-formed active-channel device exhibits extremely high response values (>2000% at 10 ppm) for NO2 along with excellent NO2 selectivity. Moreover, the NO2 gas response of the gas sensing device with vertically self-formed SnS2 nanosheets is more than two orders of magnitude higher than that of a similar exfoliated SnS2 -based device. These results indicate that the facile device fabrication method would be applicable to various systems in which surface area plays an important role.

Comparison of spin-echo echoplanar imaging and gradient recalled echo-based MR elastography at 3 Tesla with and without gadoxetic acid administration.

OBJECTIVE: To compare spin-echo echoplanar imaging (SE-EPI) and gradient recalled echo (GRE) MR elastography (MRE) at 3 T with and without gadoxetic acid administration. METHODS: We included 84 patients who underwent MRE before and after gadoxetic acid administration, each time using SE-EPI and GRE sequences. Diagnostic performance for predicting clinical liver cirrhosis and high-risk oesophageal varices was assessed using the area under the receiver-operating characteristic curve (AUC). The relationships between T2* and success of MRE, and correlations of liver stiffness (LS) values between the two sequences or before and after gadoxetic acid administration, were investigated. RESULTS: SE-EPI-MRE resulted in a significantly lower failure rate than GRE-MRE (1.19% vs. 10.71%, P = 0.018). Increased T2* was related to higher probability of successful LS measurement (odds ratio, 1.426; P = 0.004). The AUC of SE-EPI-MRE was comparable to that of GRE-MRE for the detection of clinical liver cirrhosis (0.938 vs. 0.948, P = 0.235) and high-risk oesophageal varices (0.839 vs. 0.752, P = 0.354). LS values were not significantly different before and after gadoxetic acid administration. CONCLUSION: SE-EPI-MRE can substitute for GRE-MRE for the detection of clinical liver cirrhosis and high-risk oesophageal varices. SE-EPI-MRE is particularly useful in patients with iron deposition, with lower failure rates than GRE-MRE. KEY POINTS: • LS values are comparable between SE-EPI-MRE and GRE-MRE. • Administration of gadoxetic acid does not influence LS measurement. • The failure rate of SE-EPI-MRE is significantly lower than that of GRE-MRE.

Cancer related gene alterations can be detected with next-generation sequencing analysis of bile in diffusely infiltrating type cholangiocarcinoma.

Genome-wide association study in diffusely infiltrating type cholangiocarcinoma (CC) can be limited due to the difficulty of obtaining tumor tissue. We aimed to evaluate the genomic alterations of diffusely infiltrating type CC using next-generation sequencing (NGS) of bile and to compare the variations with those of mass-forming type CC. A total of 24 bile samples obtained during endoscopic retrograde cholangiopancreatography (ERCP) and 17 surgically obtained tumor tissue samples were evaluated. Buffy coat and normal tissue samples were used as controls for a somatic mutation analysis. After extraction of genomic DNA, NGS analysis was performed for 48 cancer related genes. There were 27 men and 14 women with a mean age of 65.0±11.8years. The amount of extracted genomic DNA from 3cm(3) of bile was 66.0±84.7µg and revealed a high depth of sequencing coverage. All of the patients had genomic variations, with an average number of 19.4±2.8 and 22.3±3.3 alterations per patient from the bile and tumor tissue, respectively. After filtering process, damaging SNPs (8 sites for each type of CC) were predicted by analyzing tools, and their target genes showed relevant differences between the diffusely infiltrating and mass-forming type CC. Finally, in somatic mutation analysis, tumor-normal paired 14 tissue and 6 bile samples were analyzed, genomic alterations of EGFR, FGFR1, ABL1, PIK3CA, and CDKN2A gene were seen in the diffusely infiltrating type CC, and TP53, KRAS, APC, GNA11, ERBB4, ATM, SMAD4, BRAF, and IDH1 were altered in the mass-forming type CC group. STK11, GNAQ, RB1, KDR, and SMO genes were revealed in both groups. The NGS analysis was feasible with bile sample and diffusely infiltrating type CC revealed genetic differences compared with mass-forming type CC. Genome-wide association study could be performed using bile sample in the patients with CC undergoing ERCP and a different genetic approach for accurate diagnosis, pathogenesis study, and targeted therapy will be needed in diffusely infiltrating type CC.

Should Assessment of Quality Indicator of Colonoscopy Be Varied Depending on the Colonoscopic Technique Level?

BACKGROUND/AIM: The purpose of this research was to evaluate if withdrawal time is a useful index in spite of differences in gastroenterologists' ability and if there are other quality indicators of colonoscopy. METHODS: A total of 665 consecutive, asymptomatic individuals of average risk between 50 and 75 years of age who underwent screening colonoscopies performed by 12 gastroenterologists were included in this study. The endoscopists were classified to either the experienced group (group A, N = 6) or the under-experienced group (group B, N = 6). The endoscopists were unaware that they were being studied during the two-month study period. RESULTS: In group A, adenoma detection rate was 0.56, while in group B it was 0.43 (P = 0.048). The mean withdrawal time ranged widely from 4.2 to 10.3 min per patient with a mean value of 6.83 for group A and 6.54 for group B. There was a significantly positive relationship between the number of adenomas detected and the withdrawal time for group B (r = 0.827, P = 0.005), but not for group A (r = -0.152, P = 0.584). In the case of group A, the ratio of cecal intubation time to withdrawal time (I/E ratio) less than 1 showed significantly correlated adenoma detection rate compared to I/E ratio greater than 1 (r = -0.308, P = 0.036). In the case of group B, mean I/E ratio was 1.7 and all endoscopists' I/E ratios were greater than 1. CONCLUSIONS: For experienced endoscopists, a useful supplementary quality indicator of colonoscopy is to keep intubation/withdrawal time ratio less than 1 and it is necessary for under-experienced endoscopists to try to keep enough withdrawal time.

Long-term efficacy of entecavir plus adefovir combination therapy versus entecavir monotherapy in adefovir refractory chronic hepatitis B patients with prior lamivudine resistance.

OBJECTIVES: We investigated the long-term efficacy of entecavir (ETV) + adefovir (ADV) combination therapy versus ETV monotherapy in lamivudine (LAM)-resistant chronic hepatitis B (CHB) patients who failed to respond to ADV rescue therapy. METHODS: A total of 91 ADV refractory patients with prior LAM resistance received ETV (1.0 mg/day) + ADV (10 mg/day) combination therapy (group A, n = 45) or ETV (1.0 mg/day) monotherapy (group B, n = 46) for more than 48 weeks. RESULTS: The rates of undetectable serum hepatitis B virus DNA levels (≤20 IU/ml) at weeks 48 and 96 were not significantly different between group A and group B (31.1 vs. 23.9% at week 48, p = 0.442, and 44.7 vs. 34.5% at week 96, p = 0.457). However, the incidence of virological breakthrough in group A was significantly lower than that in group B (0 vs. 17.4% at week 48, p = 0.006, and 2.6 vs. 44.8% at week 96, p < 0.001). ETV monotherapy was the only independent factor significantly associated with virologic breakthrough (p = 0.015). CONCLUSIONS: ETV + ADV combination therapy is a better therapeutic option than ETV monotherapy for ADV refractory CHB patients with prior LAM resistance.

Pancreatic hyperenzymemia is associated with bacterial culture positivity, more severe and right-sided colitis.

BACKGROUND/AIM: Several studies reported pancreatic hyperenzymemia (PHE) related to acute colitis. However, there is no consensus on its clinical significance. This study was addressed to find the clinical significance of PHE in acute colitis. METHODS: Pancreatic hyperenzymemia was defined as abnormal increase in serum concentrations of the pancreatic enzymes by three times of normal upper range without definite pancreatic symptoms and evidence of pancreatitis at abdominal CT imaging of pancreatic disease. And clinical and laboratory and biologic parameters of PHE group and normal pancreatic enzymemia (NPE) group were compared. RESULTS: A total of 1,069 patients admitted to hospitals due to acute colitis were analyzed. Of these patients, 2.99 % (32/1,069) showed PHE. PHE group showed more severe symptoms and had longer hospital stays than the NPE group (12.15 vs. 4.59 days; P < 0.001). Multivariable analysis showed that right-sided colitis (OR 2.846; 95 % CI 1.122-7.224; P = 0.028) and culture positivity (OR 3.346; 95 % CI 1.119-10.008; P = 0.031) are associated with PHE during acute colitis. Also, PHE group was more common when a microorganism could be identified in the cultures (28.1 vs. 7.0 %; P = 0.003), especially blood culture. Among patients with positive cultures, Salmonella spp. had a positive correlation with the right-sided colitis and PHE (amylase P = 0.002; lipase P = 0.029), Salmonella serovar typhimurium (group B) was especially related to increased serum lipase but not to increased serum amylase (lipase; P = 0.041: amylase; P = 0.485). CONCLUSION: Pancreatic hyperenzymemia is associated with right-sided colitis, bacterial culture positivity, and severe acute colitis.

Full automation of point defect detection in transition metal dichalcogenides through a dual mode deep learning algorithm.

Point defects often appear in two-dimensional (2D) materials and are mostly correlated with physical phenomena. The direct visualisation of point defects, followed by statistical inspection, is the most promising way to harness structure-modulated 2D materials. Here, we introduce a deep learning-based platform to identify the point defects in 2H-MoTe2: synergy of unit cell detection and defect classification. These processes demonstrate that segmenting the detected hexagonal cell into two unit cells elaborately cropped the unit cells: further separating a unit cell input into the Te2/Mo column part remarkably increased the defect classification accuracies. The concentrations of identified point defects were 7.16 × 1020 cm2 of Te monovacancies, 4.38 × 1019 cm2 of Te divacancies and 1.46 × 1019 cm2 of Mo monovacancies generated during an exfoliation process for TEM sample-preparation. These revealed defects correspond to the n-type character mainly originating from Te monovacancies, statistically. Our deep learning-oriented platform combined with atomic structural imaging provides the most intuitive and precise way to analyse point defects and, consequently, insight into the defect-property correlation based on deep learning in 2D materials.

Atomistic Probing of Defect-Engineered 2H-MoTe2 Monolayers.

Point defects dictate various physical, chemical, and optoelectronic properties of two-dimensional (2D) materials, and therefore, a rudimentary understanding of the formation and spatial distribution of point defects is a key to advancement in 2D material-based nanotechnology. In this work, we performed the demonstration to directly probe the point defects in 2H-MoTe2 monolayers that are tactically exposed to (i) 200 °C-vacuum-annealing and (ii) 532 nm-laser-illumination; and accordingly, we utilize a deep learning algorithm to classify and quantify the generated point defects. We discovered that tellurium-related defects are mainly generated in both 2H-MoTe2 samples; but interestingly, 200 °C-vacuum-annealing and 532 nm-laser-illumination modulate a strong n-type and strong p-type 2H-MoTe2, respectively. While 200 °C-vacuum-annealing generates tellurium vacancies or tellurium adatoms, 532 nm-laser-illumination prompts oxygen atoms to be adsorbed/chemisorbed at tellurium vacancies, giving rise to the p-type characteristic. This work significantly advances the current understanding of point defect engineering in 2H-MoTe2 monolayers and other 2D materials, which is critical for developing nanoscale devices with desired functionality.

Vaseline gauze packing for the treatment of acute hemorrhagic rectal ulcer: Two case reports.

RATIONALE: Acute hemorrhagic rectal ulcer (AHRU) is a relatively rare condition characterized by sudden onset, painlessness, and massive hematochezia in patients with severe underlying conditions. When AHRU is encountered, they can often be successfully controlled endoscopically, though recurrent bleeding is common and an alternative treatment must be sought if initial endoscopic treatment fails. We report 2 cases of AHRU which were successfully treated with Vaseline gauze packing after the failure of endoscopic hemostasis. PATIENT CONCERNS: The first patient was an 88-year-old female that visited our emergency department with hematochezia. She was immobilized because of a left pelvic bone fracture resulting from a slip-down. The initial endoscopy showed fresh blood in her rectum with diffuse ulceration near the dentate line but no active bleeding. However, Massive hematochezia has recurred during conservation. A second patient, an 86-year-old female, debilitated because of schizophrenia, dementia, and past subdural hemorrhage, visited our emergency department, also with massive hematochezia. Her initial endoscopy showed deep ulceration near the dentate line. After admission, she experienced massive hematochezia from an AHRU with an exposed vessel but endoscopic hemostasis failed to control bleeding. DIAGNOSES: Both patients were diagnosed as AHRU based on the endoscopic findings. INTERVENTIONS: In both cases, Vaseline gauze packing was performed for bleeding control. OUTCOMES: After Vaseline gauze packing, no further bleeding occurred and follow-up endoscopy showed definitive improvement of ulcers. LESSONS: Based on these cases, we suggest that Vaseline gauze packing may be the alternative treatment for the AHRU which is located near the dentate line when endoscopic hemostasis is difficult or failed. Although further research is needed, Vaseline gauze packing has several potential advantages for the treatment of AHRU, especially in cases involving critically ill elderly patients.

Atomically Thin Synapse Networks on Van Der Waals Photo-Memtransistors.

A new type of atomically thin synaptic network on van der Waals (vdW) heterostructures is reported, where each ultrasmall cell (≈2 nm thick) built with trilayer WS2 semiconductor acts as a gate-tunable photoactive synapse, i.e., a photo-memtransistor. A train of UV pulses onto the WS2 memristor generates dopants in atomic-level precision by direct light-lattice interactions, which, along with the gate tunability, leads to the accurate modulation of the channel conductance for potentiation and depression of the synaptic cells. Such synaptic dynamics can be explained by a parallel atomistic resistor network model. In addition, it is shown that such a device scheme can generally be realized in other 2D vdW semiconductors, such as MoS2 , MoSe2 , MoTe2 , and WSe2 . Demonstration of these atomically thin photo-memtransistor arrays, where the synaptic weights can be tuned for the atomistic defect density, provides implications for a new type of artificial neural networks for parallel matrix computations with an ultrahigh integration density.

Initial treatment response and short-term mortality of spontaneous bacterial peritonitis in cirrhotic patients with hepatocellular carcinoma.

This study aimed to investigate the initial treatment response and short-term mortality of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with hepatocellular carcinoma (HCC) compared with those without HCC. A total of 245 patients with liver cirrhosis diagnosed with SBP between January 2004 and December 2020 were included. Of these, 107 (43.7%) were diagnosed with HCC. Overall, the rates of initial treatment failure, 7-day and 30-day mortality were 91 (37.1%), 42 (17.1%), and 89 (36.3%), respectively. While the baseline CTP score, MELD score, culture-positive rate, and rates of antibiotic resistance did not differ between both groups, patients with HCC had a higher rate of initial treatment failure than those without HCC patients (52.3% vs. 25.4%, P < 0.001). Similarly, 30-day mortality was also significantly higher in patients with HCC (53.3% vs. 23.2%, P < 0.001). In the multivariate analysis, HCC, renal impairment, CTP grade C, and antibiotic resistance were independent factors for initial treatment failure. Furthermore, HCC, hepatic encephalopathy, MELD score, and initial treatment failure were independent risk factors for 30-day mortality, with statistically significant poor survival outcomes in patients with HCC (P < 0.001). In conclusion, HCC is an independent risk factor for initial treatment failure and high short-term mortality in patients with cirrhosis with SBP. It has been suggested that more attentive therapeutic strategies are required to improve the prognosis of patients with HCC and SBP.

Efficacy and safety of CKD-495 in acute and chronic gastritis: A Phase III superiority clinical trial.

BACKGROUND: Despite the availability of numerous treatment options, many patients with gastritis experience only partial symptom relief. CKD-495, a newly developed product with the active ingredient extracted from Cinnamomum cassia Presl., has demonstrated anti-inflammatory and antioxidant activity in vitro and an in vivo protective effect against gastric damage by stimulating mucus secretion. This study compared the efficacy and safety of CKD-495 with Artemisiae argyi folium (AAF) for the treatment of acute and chronic gastritis. AAF, a gastric mucosa protective agent that promotes gastric mucosa regeneration, has been used clinically for about 20 years. METHODS: This phase III multicenter, randomized, double-blind, parallel-group trial (ClinicalTrials.gov; NCT04255589) assigned 242 patients with endoscopically-proven gastric mucosal erosions to receive CKD-495 75 mg (n = 122) or AAF 60 mg (n = 120), respectively, with placebo (for double-blind purposes) 3 times a day for 2 weeks. The primary efficacy endpoint was the erosion improvement rate. Secondary endpoints included erosion cure rates, and improvement rates for edema, redness, hemorrhage, and gastrointestinal (GI) symptoms. Drug-related adverse events were evaluated. RESULTS: The erosion improvement rate was significantly higher in the CKD-495 group than in the AAF group for both the full analysis set (55.9% vs 39.4%, P = .0063) and per-protocol set (54.6% vs 38.2%, P = .0084). In addition, the erosion improvement rate in patients with acute or chronic gastritis showed that the CKD-495 group had better improvement of erosion than the AAF group, especially in patients with chronic gastritis. Analysis of secondary endpoints, which included erosion cure rate and the improvement rates of edema, redness, hemorrhage, and GI symptoms, showed that the CKD-495 group was more effective than the AAF group. There were no significant between-group differences in safety profiles. No serious adverse events or adverse drug reactions occurred. CONCLUSIONS: These results demonstrate that CKD-495 75 mg is superior to AAF 60 mg in terms of the endoscopic improvement rate of erosions in patients with acute or chronic gastritis. This new mucoprotective agent, CKD-495, can be considered the therapy of choice for symptomatic relief and healing of gastritis.