Pharmacokinetics, pharmacodynamics and safety of oral formulation (CG-750) of ivaltinostat, a histone deacetylase inhibitor, compared to IV formulation (CG-745).

AIMS: CG-750 is an oral formulation of ivaltinostat, a newly developing histone deacetylase (HDAC) inhibitor. This study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of an oral formulation (CG-750) of ivaltinostat compared to an intravenous (IV) formulation (CG-745). METHODS: A randomized, double-blind, placebo-controlled study was conducted in three cohorts. Subjects received either CG-745 (Cohorts 1 and 3: 125 mg; Cohort 2: 250 mg) or placebo followed by CG-750 (Cohort 1: 125 mg; Cohort 2: 375 mg; Cohort 3: 750 mg) or placebo. Blood samples for PK and PD assessment were collected up to 72 h post-dose. Histone H3 acetylation at sites K9, K9/K14 and K27 was assessed for area under the % acetylation induction versus time curve (AUEC). RESULTS: A total of 25 subjects were randomized, and 23 subjects completed the study (Cohort 1, n = 6; Cohort 2, n = 6; Cohort 3, n = 6; placebo, n = 5). The mean bioavailability of CG-750 was 10.6% (range: 4.18%-21.33%) and displayed linear PK in the dose range of 125-750 mg. The comparison of AUEC between formulations and the evaluation of the dose-AUEC relationship were inconclusive, due to the small sample sizes and significant variability observed in PD markers. All adverse events (AEs) were transient and of mild or moderate intensity. CONCLUSIONS: The oral formulation of ivaltinostat (CG-750) was generally well tolerated after a single dose. CG-750 displayed a mean bioavailability of 10.6%.

Detection of Clarithromycin Resistance in Helicobacter pylori Using MmaxSure™ H. pylori & ClaR Assay.

INTRODUCTION: Clarithromycin resistance is a crucial factor in the eradication of Helicobacter pylori. This study aimed to evaluate the performance of MmaxSure™ H. pylori & ClaR Assay (MmaxSure™) in the diagnosis and detection of clarithromycin resistance in H. pylori. METHODS: Subjects who underwent esophagogastroduodenoscopy between April 2020 and October 2022 were enrolled. The diagnostic performances of MmaxSure™ and dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) were compared with the rapid urease test and culture. Secondary gene sequencing analysis was performed in discordant cases of PCR tests. RESULTS: A total of 156 gastric biopsy samples were analyzed. In H. pylori detection, MmaxSure™ showed a 95.9% sensitivity (95% CI: 90.6-98.6), a 42.7% specificity (95% CI: 26.3-60.7), and a kappa value of 0.457. For the detection of A2143G mutation samples, MmaxSure™ showed a 91.2% sensitivity (95% CI: 76.3-98.1), a 93.4% specificity (95% CI: 87.5-97.1), and a kappa value of 0.804. There were a total of 10 discordant cases compared to gene sequencing in A2143G mutation detection for MmaxSure™. CONCLUSION: In this study, MmaxSure™ showed comparable diagnostic performance to DPO-PCR in the detection of the H. pylori and A2143G mutation. Further research is needed to confirm the clinical effectiveness of the MmaxSure™ assay in H. pylori eradication.

Loss of Inpp5d has disease-relevant and sex-specific effects on glial transcriptomes.

INTRODUCTION: Inpp5d is genetically associated with Alzheimer's disease risk. Loss of Inpp5d alters amyloid pathology in models of amyloidosis. Inpp5d is expressed predominantly in microglia but its function in brain is poorly understood. METHODS: We performed single-cell RNA sequencing to study the effect of Inpp5d loss on wild-type mouse brain transcriptomes. RESULTS: Loss of Inpp5d has sex-specific effects on the brain transcriptome. Affected genes are enriched for multiple neurodegeneration terms. Network analyses reveal a gene co-expression module centered around Inpp5d in female mice. Inpp5d loss alters Pleotrophin (PTN), Prosaposin (PSAP), and Vascular Endothelial Growth Factor A (VEGFA) signaling probability between cell types. DISCUSSION: Our data suggest that the normal function of Inpp5d is entangled with mechanisms involved in neurodegeneration. We report the effect of Inpp5d loss without pathology and show that this has dramatic effects on gene expression. Our study provides a critical reference for researchers of neurodegeneration, allowing separation of disease-specific changes mediated by Inpp5d in disease from baseline effects of Inpp5d loss. HIGHLIGHTS: Loss of Inpp5d has different effects in male and female mice. Genes dysregulated by Inpp5d loss relate to neurodegeneration. Total loss of Inpp5d in female mice collapses a conserved gene co-expression module. Loss of microglial Inpp5d affects the transcriptome of other cell types.

Quantitative multiplex real-time polymerase chain reaction assay for the detection of Helicobacter pylori and clarithromycin resistance.

BACKGROUND: Identifying clarithromycin resistance is essential for eradicating Helicobacter pylori (HP). Therefore, we evaluated the performance of Allplex™ H.pylori & ClariR Assay (Allplex™) for diagnosing and detecting clarithromycin resistance in HP. METHODS: Subjects who underwent esophagogastroduodenoscopy between April 2020 and August 2021 at Incheon St. Mary's hospital were enrolled in this study. The diagnostic performances of Allplex™ and dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) were compared with sequencing as the gold standard. RESULTS: A total of 142 gastric biopsy samples were analyzed. Gene sequencing revealed 124 HP infections, 42 A2143G mutations, 2 A2142G mutations, one dual mutation, and no A2142C mutation. DPO-PCR showed 96.0% sensitivity and 100.0% specificity for HP detection; the corresponding rates for Allplex™ were 99.2% and 100.0%. DPO-PCR showed 88.3% sensitivity and 82.0% specificity for A2143G mutation, and Allplex™ showed 97.6% and 96.0%. The Cohen's Kappa coefficient for overall test results was 0.56 for DPO-PCR and 0.95 for Allplex™. CONCLUSION: Allplex™ showed comparable diagnostic performance with direct gene sequencing and non-inferior diagnostic performance to DPO-PCR. Further research is required to confirm whether Allplex™ is an effective diagnostic tool for the eradication of HP.

Effect of haemodialysis on the pharmacokinetics and pharmacodynamics of evogliptin.

AIM: To investigate the possible effect of haemodialysis (HD) on the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of evogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor. METHODS: A single-dose, open-label, parallel-group study of eight end-stage renal disease (ESRD) patients and eight matched healthy subjects was conducted. ESRD patients received a single oral dose of evogliptin 5 mg after and before HD with a 2-week washout between each dose, and healthy subjects received a single oral dose of evogliptin 5 mg. Serial blood, dialysate, and urine samples were collected to assess the PK and PD profiles of evogliptin. To compare PK parameters before and after HD, geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were calculated. RESULTS: The GMRs for the maximum concentration and area under the concentration-time curve from time 0 to the last measurable timepoint (AUClast ) of evogliptin when administered before HD compared with after HD were 0.7293 (90% CI 0.6171-0.8620) and 0.9480 (90% CI 0.8162-1.1010), respectively. The maximum DPP-4 inhibitory effect, area under the DPP-4 inhibitory effect-time curve, and time duration of more than 80% DPP-4 inhibition were comparable when evogliptin was administered before and after HD. Compared with healthy subjects, the mean AUClast of evogliptin was approximately 1.4-fold greater in ESRD patients, but the difference is unlikely to affect the safety and efficacy of evogliptin. CONCLUSION: The effect of HD on the PK and PD characteristics of evogliptin was not clinically significant; therefore, dose adjustment according to HD status is not necessary.

Pharmacokinetic and pharmacodynamic exploration of various combinations of tegoprazan immediate and delayed-release formulations.

AIMS: The new modified-release formulation of tegoprazan, a novel potassium-competitive acid blocker, is expected to improve the management of acid-related disease, including nocturnal acid breakthrough, by prolonging the duration of acid suppression. This study aimed to explore the pharmacokinetics (PK) and pharmacodynamics (PD) of various combinations of tegoprazan with immediate-release (IR) and delayed-release (DR) formulations. METHODS: A three-cohort, open-label, randomized, single-dose, three-treatment, six-sequence, three-period crossover study was conducted. Various combinations of tegoprazan IR and DR formulations (50, 75 or 100 mg) were administered orally once per period. The 24-h intragastric pH was monitored before and after each administration. PK blood samples were collected for up to 48 h. PK and PD were compared among treatments. RESULTS: Eighteen healthy Korean subjects completed the study. All treatment groups showed intragastric pH above 4 approximately 1 h following tegoprazan administration. Among the various combinations, the IR and DR combination at a 1:1 ratio induced greater gastric acid suppression (%Time pH ≥ 4) than IR alone in each dose group, both for 24 h (50 mg; 59% vs. 52%, P = .2188, 95% confidence interval [CI] -6.92-22.27, 100 mg; 85% vs. 70%, P < .05, 95% CI 8.92-22.19) and at night (50 mg; 27% vs. 16%, P = .1563, 95% CI -11.79-37.71, 100 mg; 77% vs. 49%, P < .05, 95% CI 16.14-42.98), with similar systemic exposure. CONCLUSIONS: The combinatorial tegoprazan in the IR and DR 1:1 ratio formulation was found to induce stronger gastric acid suppression throughout the day and at night, compared to the conventional IR formulation.

Pharmacokinetic and pharmacodynamic interaction between DWP16001, an sodium-glucose cotransporter 2 inhibitor and metformin in healthy subjects.

AIMS: DWP16001 is a novel sodium-glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes with selective and sustained sodium-glucose cotransporter 2 inhibition. We aimed to evaluate whether the coadministration of DWP16001 and metformin causes any changes in pharmacokinetics (PK) or pharmacodynamics (PD). METHODS: A randomized, open-label, single- and multiple-dose, 2-sequence, crossover study was conducted in healthy male subjects. Subjects received the following treatments: a single oral dose of DWP16001 (DWP) 2 mg, metformin immediate release 1000 mg (MET) twice daily for 7 days and a single oral dose of DWP and MET at steady-state for metformin (DWP+MET). Serial blood and interval urine were collected for PK and PD analyses. Safety and tolerability profiles were assessed throughout the study. RESULTS: DWP+MET displayed increased peak concentration and area under the concentration-time curve from time 0 to time of the last quantifiable concentration compared with DWP (per standard bioequivalence boundaries, 0.8-1.25); the geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) were 1.22 (1.13-1.31) and 1.09 (1.05-1.14), respectively. DWP+MET and MET showed similar peak concentration and area under the concentration-time curve within a dosing interval at steady state for metformin; the GMRs and 90% CIs were 0.98 (0.90-1.06) and 1.05 (0.98-1.13), respectively. The amount of urinary glucose excretion from time 0 to 144 h was also comparable between DWP+MET and DWP (GMR and 90% CI; 0.99, 0.94-1.05). CONCLUSION: The results suggest that DWP16001 and metformin could be coadministered without clinically relevant PK and PD interactions.

Efficacy of bougie dilation for normal diet in benign esophageal stricture.

OBJECTIVES: Bougination is one of the first-line treatments in benign esophageal stricture (BES). The aim of the study was to identify clinical and endoscopic factors affecting the achievement of a normal diet with only bougie dilation in patients with BES. PATIENTS AND METHODS: Patients treated with only bougination for BES at three hospitals were retrospectively investigated. Data including patient demographics, stricture and procedural characteristics were collected. Clinical success was defined as normal diet without additional procedures for two months after bougination. Clinical success rate and associated factors were assessed. RESULTS: A total of 121 patients with BES were included. The most common cause of BES was post-operative stricture (n = 55). Finally, 43 (36%) patients were able to eat a normal diet with only bougination. Of these patients, 42 (97.7%) achieved clinical success in the first three sessions or less. Among causes of stenosis, corrosive injury had the lowest success rate (9/40, 22.5%). Clinical success rate was significantly higher for those with the length of stricture of less than 2 cm (47.2%), those with pre-procedural dysphagia of semi-solid or soft diet (51.3%) and those with dilation of 13 mm or more (46.1%). However, the duration of symptom, the number of previous endoscopic treatments and the location of stenosis were not related to clinical success. CONCLUSIONS: Normal diet is possible in one-third of BES after bougination alone. Predictable factors for achieving a normal diet were less than four sessions of dilation, short length of stricture, pre-procedural dysphagia status and diameter of dilator.

The optimal interval of surveillance gastroscopy after endoscopic resection for gastric neoplasia: a multicenter cohort study.

BACKGROUND/AIMS: Due to the possible metachronous recurrence of gastric neoplasia, surveillance gastroscopy is mandatory after endoscopic resection for gastric neoplasia. However, there is no consensus on the surveillance gastroscopy interval. This study aimed to find an optimal interval of surveillance gastroscopy and to investigate the risk factors for metachronous gastric neoplasia. METHODS: Medical records were reviewed retrospectively in patients who underwent endoscopic resection for gastric neoplasia in 3 teaching hospitals from June 2012 to July 2022. Patients were divided into two groups; annual surveillance vs. biannual surveillance. The incidence of metachronous gastric neoplasia was identified, and the risk factors for metachronous gastric neoplasia were investigated. RESULTS: Among the 1,533 patients who underwent endoscopic resection for gastric neoplasia, 677 patients were enrolled in this study (annual surveillance 302, biannual surveillance 375). Metachronous gastric neoplasia was observed in 61 patients (annual surveillance 26/302, biannual surveillance 32/375, P = 0.989), and metachronous gastric adenocarcinoma was observed in 26 patients (annual surveillance 13/302, biannual surveillance 13/375, P = 0.582). All the lesions were removed by endoscopic resection successfully. In a multivariate analysis, severe atrophic gastritis on gastroscopy was an independent risk factor for metachronous gastric adenocarcinoma (odds ratio 3.8, 95% confidence interval 1.4‒10.1; P = 0.008). CONCLUSIONS: Meticulous observation to detect the metachronous gastric neoplasia is necessary for patients with severe atrophic gastritis during follow-up gastroscopy after endoscopic resection for gastric neoplasia. Annual surveillance gastroscopy might be enough after endoscopic resection for gastric neoplasia.

Cold snare polypectomy versus cold endoscopic mucosal resection for small colorectal polyps: a multicenter randomized controlled trial.

BACKGROUND: Cold snare polypectomy (CSP) is recommended for the resection of small colorectal polyps. However, few studies have investigated the efficacy of cold endoscopic mucosal resection (cold EMR) for small polyps. Thus, the aim of this study was to investigate the efficacy and safety of cold EMR compared with CSP for small colorectal polyps. METHODS: This was a multicenter, randomized trial conducted in three tertiary centers from January 2018 to February 2021. Patients with polyps sized 6-10 mm were randomized to CSP or cold EMR group. After polypectomy, two additional biopsies were performed to assess the completeness of resection. The primary outcome was complete polyp resection rate. Secondary outcomes were total procedure time and rate of adverse events such as immediate bleeding, delayed bleeding, and perforation. RESULTS: A total of 444 polyps in 327 patients were assessed and randomly assigned to each group. Of those, 425 polyps were finally analyzed based on pathology results. The complete resection rate was not significantly different between cold EMR and CSP groups (91.9% vs 89.8%, p = 0.24). However, the total procedure time was significantly increased in cold EMR (87.6 s vs. 45.8 s, p < 0.001). The rate of polypectomy adverse events was not significantly different between the two groups. No patient had massive bleeding or perforation. CONCLUSIONS: There was no difference in complete resection rate or adverse events between CSP and cold EMR. However, CSP reduced the total procedure time.

Evaluation of Vancomycin TDM Strategies: Prediction and Prevention of Kidney Injuries Based on Vancomycin TDM Results.

The current guidelines for therapeutic drug monitoring (TDM) of vancomycin suggest a target 24-hour area under the curve (AUC0-24) of 400 to 600 mg*h/L for serious methicillin-resistant Staphylococcus aureus infections. In this study, the predictabilities of acute kidney injury (AKI) of various TDM target parameters, target levels, and sampling methods were evaluated in patients who underwent TDM from January 2020 to December 2020. The AUC0-24 and trough values were calculated by both one- and two-point sampling methods, and were evaluated for the predictability of AKI. Among the AUC0-24 cutoff comparisons, the threshold value of 500 mg*h/L in the two sampling methods was statistically significant (P = 0.042) when evaluated for the predictability of AKI. Analysis by an receiver operating characteristic curve estimated an AUC0-24 cutoff value of 563.45 mg*h/L as a predictor of AKI, and was proposed as the upper limit of TDM target.

Combination of Enhanced Instructions Improve Quality of Bowel Preparation: A Prospective, Colonoscopist-Blinded, Randomized, Controlled Study.

BACKGROUND: Appropriate bowel preparation is highly important for the efficacy of colonoscopy; however, up to one-third of patients do not accomplish adequate bowel preparation. OBJECTIVE: We investigated the impact of the combination of enhanced instruction on the quality of bowel preparation and its impact on clinically relevant outcomes. DESIGN: This was a colonoscopist-blinded, prospective, randomized trial. SETTINGS: All patients received regular instructions for bowel preparation. Patients were randomly assigned to the control, telephone reeducation, and combined enhanced instruction groups. PATIENTS: Outpatients aged 19 to 75 years scheduled to undergo colonoscopy were included. MAIN OUTCOME MEASURES: The main outcome was adequate bowel preparation rate. RESULTS: A total of 311 patients were randomly assigned to the combined enhanced instruction (n = 104), telephone reeducation (n = 101), and control groups (n = 106). An intention-to-treat analysis showed that the adequate bowel preparation rate was higher in the combined enhanced instruction group than in the telephone reeducation and control groups (92.3% vs 82.2% vs 76.4%, p = 0.007). The rate of compliance with the instructions was significantly higher in the combined enhanced instruction group than in the telephone reeducation and control groups. Method of education was associated with proper bowel preparation (adjusted OR 17.46; p < 0.001 for combined enhanced instruction relative to control). LIMITATIONS: This was a single-center study conducted in Korea. CONCLUSIONS: Combined enhanced instruction as an adjunct to regular instructions much improved the quality of bowel preparation and patients' adherence to the preparation instructions. The combined enhanced instruction method could be the best option for bowel preparation instruction. See Video Abstract at http://links.lww.com/DCR/B673. LA COMBINACIN DE INSTRUCCIONES MEJORADAS, INCREMENTA LA CALIDAD DE LA PREPARACIN INTESTINAL ESTUDIO PROSPECTIVO, CONTROLADO, ALEATORIO Y CIEGO PARA EL COLONOSCOPISTA: ANTECEDENTES:La preparación adecuada del intestino es muy importante para la eficacia de la colonoscopia; sin embargo, hasta un tercio de los pacientes no logran buenos resutlados.OBJETIVO:Investigar el impacto de la combinación de instrucciónes claras en la calidad de la preparación intestinal y su impacto en los resultados clínicos.DISEÑO:Trabajo aleatorio, prospectivo y ciego para el colonoscopista.AJUSTES:Los pacientes recibieron instrucciones periódicas para la preparación intestinal. Fueron asignados aleatoriamente al grupo control, educación telefónica y de instrucción mejoradas.PACIENTES:Se incluyeron pacientes ambulatorios de 19 a 75 años programados para ser sometidos a colonoscopia.PRINCIPALES MEDIDAS DE RESULTADO:El principal resultado fue una adecuada preparación intestinal.RESULTADOS:Un total de 311 pacientes fueron asignados al azar a la instrucción mejorada combinada (n = 104), reeducación telefónica (n = 101) y grupo de control (n = 106). El análisis estadístico mostró que la tasa de preparación intestinal adecuada fue mayor en el grupo combinado de instrucción mejorada que en los grupos de reeducación telefónica y control (92,3% vs 82,2% vs 76,4%, p = 0,007). La tasa de cumplimiento de las instrucciones fue significativamente mayor en el grupo de instrucción mejorada combinada que en los otros. El método de educación se asoció con una preparación intestinal adecuada (razón de posibilidades ajustada de 17,46; p <0,001 para la instrucción mejorada combinada en relación con el control.LIMITACIONES:Estudio en un solo centro realizado en Corea.CONCLUSIONES:La instrucción mejorada combinada como complemento de las instrucciones regulares mejoró mucho la calidad de la preparación intestinal y la adherencia de los pacientes a las instrucciones de preparación. El método de instrucción mejorado combinado podría ser la mejor opción para la instrucción de preparación intestinal. Consulte Video Resumen en http://links.lww.com/DCR/B673.

Super-Resolution Ultrasound Imaging Scheme Based on a Symmetric Series Convolutional Neural Network.

In this paper, we propose a symmetric series convolutional neural network (SS-CNN), which is a novel deep convolutional neural network (DCNN)-based super-resolution (SR) technique for ultrasound medical imaging. The proposed model comprises two parts: a feature extraction network (FEN) and an up-sampling layer. In the FEN, the low-resolution (LR) counterpart of the ultrasound image passes through a symmetric series of two different DCNNs. The low-level feature maps obtained from the subsequent layers of both DCNNs are concatenated in a feed forward manner, aiding in robust feature extraction to ensure high reconstruction quality. Subsequently, the final concatenated features serve as an input map to the latter 2D convolutional layers, where the textural information of the input image is connected via skip connections. The second part of the proposed model is a sub-pixel convolutional (SPC) layer, which up-samples the output of the FEN by multiplying it with a multi-dimensional kernel followed by a periodic shuffling operation to reconstruct a high-quality SR ultrasound image. We validate the performance of the SS-CNN with publicly available ultrasound image datasets. Experimental results show that the proposed model achieves a high-quality reconstruction of the ultrasound image over the conventional methods in terms of peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM), while providing compelling SR reconstruction time.

Propofol compared with bolus and titrated midazolam for sedation in outpatient colonoscopy: a prospective randomized double-blind study.

BACKGROUND AND AIMS: The safest and most efficient method of sedation for outpatient colonoscopy remains unclear. This study aimed to compare the efficiency and safety of bolus administration of midazolam compared with titrated administration and propofol administration for patients undergoing outpatient colonoscopy. METHODS: We randomly divided patients undergoing colonoscopy into the propofol group, bolus midazolam group, and titrated midazolam group. We compared total procedure time, induction time, recovery time, and discharge time among the 3 groups. We also compared patient satisfaction and the incidence of adverse events. RESULTS: In total, 267 patients (89 in each study group) were enrolled during the study period. Patients in the propofol group had a shorter total procedure time (39.5 vs 59.4 vs 58.1 minutes; P < .001), induction time (4.6 vs 6.3 vs 7.6 minutes; P < .001), recovery time (11.5 vs 29.5 vs 29.2 minutes; P < .001), and discharge time (20.6 vs 34.9 vs 34.7 minutes; P < .001) than patients in the bolus midazolam group and titrated midazolam group. Patients in the propofol group reported higher degrees of satisfaction than patients in the bolus or titrated midazolam plus meperidine groups (9.9 vs 9.6 vs 9.6 [P = .007] and 4.9 vs 4.7 vs 4.8 [P = .008], respectively). Adverse events were not significantly different between groups. CONCLUSIONS: In this randomized trial, propofol was superior to bolus or titrated midazolam in terms of endoscopy unit efficiency and patient satisfaction during outpatient colonoscopy. (Clinical trial registration number: KCT0002805.).

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.

Withdrawal time of 8 minutes is associated with higher adenoma detection rates in surveillance colonoscopy after surgery for colorectal cancer.

BACKGROUND & AIMS: Although several studies have been conducted on the relation between withdrawal time (WT) and adenoma detection rate (ADR) in the intact colonKim, little is known about the optimal WT needed to increase ADR in the postoperative colon. We investigated the association between WT and ADR in surveillance colonoscopy after colorectal cancer (CRC) surgery. METHODS: We conducted a retrospective cohort study of CRC patients who underwent 1st surveillance colonoscopy after curative colectomy. We excluded patients with incomplete inspection of colon during preoperative colonoscopy, inadequate bowel preparation, and total colectomy or subtotal colectomy. The colonoscopies were performed by 8 board-certified colonoscopists. The receiver operating characteristic curve of the WT revealed an optimal cutoff value of 7.8 min for adenoma detection. We divided the colonoscopists into fast and slow colonoscopists using the 8-min WT as cutoff, and compared the ADR between the two groups. RESULTS: We analyzed a total of 1341 patients underwent first surveillance colonoscopy after CRC surgery. Mean WTs by 8 colonoscopists during colonoscopy with and without polypectomy were 18.9 ± 13.7 and 8.1 ± 5.6 min, respectively. ADR varied from 29.3 to 50.6% by individual colonoscopists. Slow colonoscopists showed significantly higher ADR than fast colonoscopists (49.1% vs 32.2%, P < 0.001). The mean WT during colonoscopy without polypectomy for each colonoscopist and the detection rate of all neoplasia were positively correlated (Rs = 0.874, P = 0.005). CONCLUSION: Because patients who underwent colorectal surgery possess high risk of metachronous CRC and adenoma, sufficient WT (8-10 min) is mandatory, despite short length colon due to surgery.

Comparison of adenoma detection by colonoscopy between polypectomy performed during both insertion and withdrawal versus during withdrawal only: a multicenter, randomized, controlled trial.

BACKGROUND AND AIM: In standard colonoscopy, the colonoscope is inserted into the cecum, and inspection of the colonic mucosa and polypectomy are performed during withdrawal. The colon configuration can differ between the insertion and withdrawal phases, and some polyps found in the insertion phase can be missed during withdrawal. A few single-center studies investigated whether detection of polyps during the insertion phase affects the adenoma detection rate (ADR). However, the effectiveness of this strategy is unknown because of conflicting results. We aimed to determine whether polypectomy together with careful inspection during insertion increases the ADR compared with standard colonoscopy. METHODS: A randomized, controlled, multicenter trial was conducted at three university hospitals. Patients aged 50 to 80 years were randomly assigned to the study group or control group. For patients in the study group, polypectomy was performed together with careful inspection during both colonoscope insertion and withdrawal. In the control group, polyps were inspected and removed only during colonoscope withdrawal. The primary endpoint was the ADR, which was defined as the percentage of patients with ≥ 1 adenoma. RESULTS: A total of 1142 patients were enrolled (study group, n = 571; control group, n = 571). The ADR was similar in the 2 groups (study group, 44.1%; control group, 43.1%; P = 0.72). In the control group, 12 polyps that had been detected during colonoscope insertion were not found during withdrawal (polyp miss rate: 2.1%, 12/571). CONCLUSION: Polypectomy and careful inspection during both colonoscope insertion and withdrawal did not improve the overall ADR compared with standard colonoscopy (NCT01925833).

2-Hydroxy-4-Methylbenzoic Anhydride Inhibits Neuroinflammation in Cellular and Experimental Animal Models of Parkinson's Disease.

Microglia-mediated neuroinflammation is one of the key mechanisms involved in acute brain injury and chronic neurodegeneration. This study investigated the inhibitory effects of 2-hydroxy-4-methylbenzoic anhydride (HMA), a novel synthetic derivative of HTB (3-hydroxy-4-trifluoromethylbenzoic acid) on neuroinflammation and underlying mechanisms in activated microglia in vitro and an in vivo mouse model of Parkinson's disease (PD). In vitro studies revealed that HMA significantly inhibited lipopolysaccharide (LPS)-stimulated excessive release of nitric oxide (NO) in a concentration dependent manner. In addition, HMA significantly suppressed both inducible NO synthase and cyclooxygenase-2 (COX-2) at the mRNA and protein levels in LPS-stimulated BV-2 microglia cells. Moreover, HMA significantly inhibited the proinflammatory cytokines such as interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha in LPS-stimulated BV-2 microglial cells. Furthermore, mechanistic studies ensured that the potent anti-neuroinflammatory effects of HMA (0.1, 1.0, and 10 µM) were mediated by phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) in LPS-stimulated BV-2 cells. In vivo evaluations revealed that intraperitoneal administration of potent neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg, four times a 1 day) in mice resulted in activation of microglia in the brain in association with severe behavioral deficits as assessed using a pole test. However, prevention of microglial activation and attenuation of Parkinson's disease (PD)-like behavioral changes was obtained by oral administration of HMA (30 mg/kg) for 14 days. Considering the overall results, our study showed that HMA exhibited strong anti-neuroinflammatory effects at lower concentrations than its parent compound. Further work is warranted in other animal and genetic models of PD for evaluating the efficacy of HMA to develop a potential therapeutic agent in the treatment of microglia-mediated neuroinflammatory disorders, including PD.

Jumbo biopsy forceps versus cold snares for removing diminutive colorectal polyps: a prospective randomized controlled trial.

BACKGROUND AND AIMS: Cold snare polypectomy (CSP) and jumbo forceps polypectomy (JFP) have been shown to be effective for removing diminutive colorectal polyps (DCPs) (≤5 mm). However, no study has compared complete resection rates between CSP and JFP for DCPs. The aim of this study was to compare the efficacy and safety of JFP with CSP for the removal of DCPs. METHODS: This was a prospective randomized controlled trial from 2 tertiary-care referral centers. A total of 1003 patients were screened, and 169 patients with 196 DCPs were enrolled. The main outcome was complete polyp resection rate. RESULTS: Of 196 diminutive polyps, 177 (90.3%) were adenomatous polyps. The overall complete resection rate was 92.1% (163/177). The complete resection rate was not significantly different between JFP and CSP groups (92.0% vs 92.2%; P = .947). JFP achieved complete resection rates comparable with CSP for polyps >3 mm (90.3% vs 89.8%; P = .928). Polypectomy procedure time, tissue retrieval rate, and rate of postpolypectomy adverse events were not significantly different between the 2 groups. CONCLUSIONS: Both JFP and CSP achieved complete resection rates of >90% for DCPs. Thus, JFP may be considered for polypectomy of DCPs. (International clinical trial registry number: KCT0002805.).

Nationwide antibiotic resistance mapping of Helicobacter pylori in Korea: A prospective multicenter study.

INTRODUCTION: The eradication rates for Helicobacter pylori have decreased in Korea although the prevalence of this bacterium has also decreased. Antibiotic resistance is likely to be a crucial factor in H. pylori eradication success, and we therefore mapped these resistance patterns nationwide in Korea. MATERIALS AND METHODS: Five hundred and ninety adult subjects were prospectively enrolled from 2017 to 2018 from 15 centers across six geographic areas of Korea. A total of 580 biopsy tissues had been sampled from these patients during an upper endoscopy and were frozen at -80°C and delivered to a central laboratory. The agar dilution method was used to determine the minimum inhibitory concentration of amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, and levofloxacin for each H. pylori isolate. RESULTS: The culture success rate was 60.2% (349/580). Resistance rates against clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, and ciprofloxacin were 17.8%, 29.5%, 9.5%, 0%, 37.0%, and 37.0%, respectively. The geographic distribution of metronidazole and quinolone resistance was highly variable. Some subjects had multiple H. pylori strains in the antrum and body of the stomach and showed a heterogeneous resistance profile between these anatomic areas. The H. pylori multidrug resistance (MDR) rate was 25.2% (88/349) among amoxicillin, clarithromycin, metronidazole, tetracycline, and quinolone and 11.2% (39/349) among four of these major antibiotics except for quinolone. The Seoul and Chungcheong areas showed a relatively lower MDR rate. CONCLUSION: The antibiotic resistance of H. pylori differs by drug and geographic area in Korea. Detailed nationwide antibiotic resistance mapping is needed to develop an effective H. pylori eradication strategy.