The Potential of Molecular Remission: Tissue Neutrophil Elastase Is Better Than Histological Activity for Predicting Long-Term Relapse in Patients With Ulcerative Colitis in Endoscopic Remission.

BACKGROUND: Growing interest exists in deep remission, beyond clinical and endoscopic remission, to enhance long-term prognosis in patients with ulcerative colitis (UC). Our study aimed to evaluate the risk of relapse according to tissue expression levels of calprotectin and neutrophil elastase (NE) in patients with quiescent UC. METHODS: Rectal biopsies were performed on 218 patients with UC in clinical and endoscopic remission. Histological activity was prospectively scored using the Robarts Histological Index. Tissue calprotectin and NE levels were evaluated using immunohistochemistry. Optimal tissue calprotectin and NE cutoffs for relapse were determined using log-rank analysis. Cox proportional hazard analyses evaluated relapse risk factors. RESULTS: Tissue calprotectin and NE levels were significantly higher in patients with histological activity than in those in histological remission (P < .001). The optimal cutoffs of tissue calprotectin and NE for relapse were 10.61 and 22.08 per mm2, respectively. The 3-year clinical relapse risk was significantly lower in the low-tissue NE group than in the high-tissue NE group (P = .009); however, it did not differ between the low- and high-tissue calprotectin group (P = .094). In multivariate analyses, a low level of tissue NE expression was independently associated with a lower risk of 3-year clinical relapse (adjusted hazard ratio = 0.453, 95% confidence interval = 0.225-0.911, P = .026), unlike histological index and tissue calprotectin. CONCLUSIONS: In patients with UC who have achieved clinical and endoscopic remission, tissue expression of NE is a better predictor of long-term relapse than histological activity.

The tissue expression of neutrophil elastase is a better predictor of long-term relapse than histological activity in patients with ulcerative colitis who achieved clinical and endoscopic remission.

US Markers and Necroinflammation, Steatosis, and Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease: The iLEAD Study.

Background Attenuation coefficient (AC) and shear-wave speed (SWS) are established US markers for assessing patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while shear-wave dispersion slope (DS) is not. Purpose To assess the relationship between the multiparametric US imaging markers DS, AC, and SWS and liver histopathologic necroinflammation in patients with MASLD. Materials and Methods This international multicenter prospective study enrolled consecutive patients with biopsy-proven MASLD between June 2019 and March 2023. Before biopsy, all participants underwent multiparametric US, and measurements of DS, AC, and SWS were obtained. Multivariable linear regression analyses were performed to assess the association of clinical variables and imaging markers with pathologic findings. The diagnostic performance of imaging markers for determining inflammation grade, steatosis grade, and fibrosis stage was assessed using the area under the receiver operating characteristic curve (AUC). Results A total of 124 participants (mean age, 53 years ± 15 [SD]; 62 males) were evaluated. In multivariable regression, lobular inflammation was associated with DS (regression coefficient, 0.06; P = .02), alanine aminotransferase level (regression coefficient, 0.002; P = .002), and Hispanic or Latino ethnicity (regression coefficient, -0.68; P = .047), while steatosis was associated with AC (regression coefficient, 3.66; P < .001) and fibrosis was associated with SWS (regression coefficient, 2.02; P < .001) and body mass index (regression coefficient, 0.05; P = .02). DS achieved an AUC of 0.72 (95% CI: 0.63, 0.82) for identifying participants with inflammation grade A2 or higher (moderate to severe inflammation). AC showed excellent performance for identifying participants with grade S1 (mild) or higher steatosis (AUC, 0.92 [95% CI: 0.87, 0.97]), while SWS showed excellent performance for identifying participants with fibrosis stage F2 or higher (clinically significant fibrosis) (AUC, 0.91 [95% CI: 0.86, 0.96]). Of the three US markers, SWS showed the highest AUC (0.81 [95% CI: 0.74, 0.89]) for the diagnosis of metabolic dysfunction-associated steatohepatitis. Conclusion Of the three US imaging markers (DS, AC, and SWS), DS was most associated with lobular inflammation grade at histologic examination and demonstrated fair diagnostic performance in distinguishing moderate to severe lobular inflammation. ClinicalTrials.gov Identifier: NCT04012242 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Yin in this issue.

Real-World Application of Artificial Intelligence for Detecting Pathologic Gastric Atypia and Neoplastic Lesions.

PURPOSE: Results of initial endoscopic biopsy of gastric lesions often differ from those of the final pathological diagnosis. We evaluated whether an artificial intelligence-based gastric lesion detection and diagnostic system, ENdoscopy as AI-powered Device Computer Aided Diagnosis for Gastroscopy (ENAD CAD-G), could reduce this discrepancy. MATERIALS AND METHODS: We retrospectively collected 24,948 endoscopic images of early gastric cancers (EGCs), dysplasia, and benign lesions from 9,892 patients who underwent esophagogastroduodenoscopy between 2011 and 2021. The diagnostic performance of ENAD CAD-G was evaluated using the following real-world datasets: patients referred from community clinics with initial biopsy results of atypia (n=154), participants who underwent endoscopic resection for neoplasms (Internal video set, n=140), and participants who underwent endoscopy for screening or suspicion of gastric neoplasm referred from community clinics (External video set, n=296). RESULTS: ENAD CAD-G classified the referred gastric lesions of atypia into EGC (accuracy, 82.47%; 95% confidence interval [CI], 76.46%-88.47%), dysplasia (88.31%; 83.24%-93.39%), and benign lesions (83.12%; 77.20%-89.03%). In the Internal video set, ENAD CAD-G identified dysplasia and EGC with diagnostic accuracies of 88.57% (95% CI, 83.30%-93.84%) and 91.43% (86.79%-96.07%), respectively, compared with an accuracy of 60.71% (52.62%-68.80%) for the initial biopsy results (P<0.001). In the External video set, ENAD CAD-G classified EGC, dysplasia, and benign lesions with diagnostic accuracies of 87.50% (83.73%-91.27%), 90.54% (87.21%-93.87%), and 88.85% (85.27%-92.44%), respectively. CONCLUSIONS: ENAD CAD-G is superior to initial biopsy for the detection and diagnosis of gastric lesions that require endoscopic resection. ENAD CAD-G can assist community endoscopists in identifying gastric lesions that require endoscopic resection.

Efficacy of robot arm-assisted endoscopic submucosal dissection in live porcine stomach (with video).

Endoscopic submucosal dissection (ESD) is technically challenging and requires a high level of skill. However, there is no effective method of exposing the submucosal plane during dissection. In this study, the efficacy of robot arm-assisted tissue traction for gastric ESD was evaluated using an in vivo porcine model. The stomach of each pig was divided into eight locations. In the conventional ESD (C-ESD) group, one ESD was performed at each location (N = 8). In the robot arm-assisted ESD (R-ESD) group, two ESDs were performed at each location (N = 16). The primary endpoint was the submucosal dissection speed (mm2/s). The robot arm could apply tissue traction in the desired direction and successfully expose the submucosal plane during submucosal dissection in all lesion locations. The submucosal dissection speed was significantly faster in the R-ESD group than in the C-ESD group (p = 0.005). The blind dissection rate was significantly lower in the R-ESD group (P = 0.000). The robotic arm-assisted traction in ESD enabled a significant improvement in submucosal dissection speed, blind dissection rate which suggests the potential for making ESD easier and enhancing procedural efficiency and safety.

Gastric microbiome signature for predicting metachronous recurrence after endoscopic resection of gastric neoplasm.

BACKGROUND: Changes in gastric microbiome are associated with gastric carcinogenesis. Studies on the association between gastric mucosa-associated gastric microbiome (MAM) and metachronous gastric cancer are limited. This study aimed to identify gastric MAM as a predictive factor for metachronous recurrence following endoscopic resection of gastric neoplasms. METHOD: Microbiome analyses were conducted for 81 patients in a prospective cohort to investigate surrogate markers to predict metachronous recurrence. Gastric MAM in non-cancerous corporal biopsy specimens was evaluated using Illumina MiSeq platform targeting 16S ribosomal DNA. RESULTS: Over a median follow-up duration of 53.8 months, 16 metachronous gastric neoplasms developed. Baseline gastric MAM varied with Helicobacter pylori infection status, but was unaffected by initial pathologic diagnosis, presence of atrophic gastritis, intestinal metaplasia, or synchronous lesions. The group with metachronous recurrence did not exhibit distinct phylogenetic diversity compared with the group devoid of recurrence but showed significant difference in ß-diversity. The study population could be classified into two distinct gastrotypes based on baseline gastric MAM: gastrotype 1, Helicobacter-abundant; gastrotype 2: Akkermansia-abundant. Patients in gastrotype 2 showed higher risk of metachronous recurrence than gastrotype (Cox proportional hazard analysis, adjusted hazard ratio [95% confidence interval]: 5.10 [1.09-23.79]). CONCLUSIONS: Gastric cancer patients can be classified into two distinct gastrotype groups by their MAM profiles, which were associated with different risk of metachronous recurrence.

Randomized, Double-Blind, Active-Controlled Phase 3 Study to Evaluate Efficacy and Safety of Zastaprazan Compared With Esomeprazole in Erosive Esophagitis.

INTRODUCTION: Zastaprazan is a potent potassium-competitive acid blocker developed to treat gastroesophageal reflux disease. The aim of this study was to evaluate the efficacy and safety of zastaprazan compared with esomeprazole in patient with erosive esophagitis (EE). METHODS: A phase III, multicenter, randomized, double-blind, noninferiority clinical study was conducted with 300 subjects with confirmed EE. Subjects were randomized to receive zastaprazan 20 mg or esomeprazole 40 mg once daily up to 8 weeks. The primary end point was the cumulative proportion of subject with healed EE confirmed by endoscopy at week 8. The secondary end points included the healing rate at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were also assessed. RESULTS: In the full analysis set, the cumulative healing rate at week 8 were 97.92% (141/144) for zastaprazan and 94.93% (131/138) ( P = 0.178) for esomeprazole. The healing rate at week 4 in the zastaprazan group was higher than the esomeprazole group (95.14% [137/144] vs 87.68% [121/138]; P = 0.026). There was no significant difference between groups in healing rates (the per-protocol set) at week 8 and week 4, symptom responses, quality of life assessments, and safety profiles. In addition, serum gastrin levels increased during treatment in both groups, with a significant difference between the 2 groups ( P = 0.047), but both decreased after treatment. DISCUSSION: An 8-week therapy of zastaprazan 20 mg is noninferior to esomeprazole 40 mg in subjects with predominantly low-grade EE. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole.

Application of ultrasonographic human estimated foetal weight formulas to cynomolgus monkeys (Macaca fascicularis) at 129-132 days of gestation: A comparative study of estimated and actual birthweight.

BACKGROUND: Cynomolgus monkeys (Macaca fascicularis) are essential in biomedical research, including reproductive studies. However, the application of human estimated foetal weight (EFW) formulas using ultrasonography (USG) in these non-human primates is not well established. OBJECTIVES: This study aims to evaluate the applicability of human EFW formulas for estimating foetal weight in cynomolgus monkeys at approximately 130 days of gestation. METHODS: Our study involved nine pregnant cynomolgus monkeys. We measured foetal parameters, including biparietal diameter, head circumference, abdominal circumference and femur length using USG. The EFW was calculated using 11 human EFW formulas. The actual birthweight (ABW) was recorded following Cesarean section, the day after the EFW calculation. For comparing EFW and ABW, we employed statistical methods such as mean absolute percentage error (APE) and Bland-Altman analysis. RESULTS: The ABW ranged between 200.36 and 291.33 g. Among the 11 formulas, the Combs formula showed the lowest APE (4.3%) and highest correlation with ABW (p < 0.001). Notably, EFW and ABW differences for the Combs formula were ≤5% in 66.7% and ≤10% in 100% of cases. The Bland-Altman analysis supported these results, showing that all cases fell within the limits of agreement. CONCLUSIONS: The Combs formula is applicable for estimating the weight of cynomolgus monkey fetuses with USG at approximately 130 days of gestation. Our observations suggest that the Combs formula can be applied in the prenatal care and biomedical research of this species.

The Effect of A2 Milk on Gastrointestinal Symptoms in Comparison to A1/A2 Milk: A Single-center, Randomized, Double-blind, Cross-over Study.

ß-Casein, a major protein in cow's milk, is divided into the A1 and A2 type variants. Digestion of A1 ß-casein yields the peptide ß-casomorphin-7 which could cause gastrointestinal (GI) discomfort but A2 milk containing only A2 ß-casein might be more beneficial than A1/A2 (regular) milk. The aim of this study was to evaluate the differences in GI discomfort after ingestion of A2 milk and A1/A2 milk. A randomized, double-blind, cross-over human trial was performed with 40 subjects who experienced GI discomfort following milk consumption. For each intervention period, either A2 milk first (A2→A1/A2) or A1/A2 milk was first consumed for 2 weeks (A1/A2→A2) following a 2-week washout period. GI symptom rating scale (GSRS) scores, questionnaire for digestive symptoms, and laboratory tests including fecal calprotectin were evaluated. For symptom analysis, generalized estimating equations gamma model was used. A2 milk increased bloating (P = 0.041) and loose stools (P = 0.026) compared to A1/A2 milk in GSRS. However, A2 milk caused less abdominal pain (P = 0.050), fecal urgency (P < 0.001) and borborygmus (P = 0.007) compared to A1/A2 milk in questionnaire for digestive symptoms. In addition, fecal calprotectin also decreased or less increased after consumption of A2 milk compared to A1/A2 milk (P = 0.030), and this change was more pronounced in males (P = 0.005) than in females. There were no significant adverse reactions during the trial. A2 milk alleviated digestive discomfort in Koreans following A2 milk consumption (ClinicalTrials.gov NCT06252636 and CRIS KCT0009301).

Which interbody device minimized nonunion, subsidence, and reoperation after anterior cervical discectomy and fusion? A systematic review and meta-analysis comparing allograft versus polyetheretherketone cage.

OBJECTIVE: Nonunion and significant subsidence after anterior cervical discectomy and fusion (ACDF) are associated with poor clinical outcomes, which occasionally lead to revision surgery. Allograft and polyetheretherketone (PEEK) cages are the two most commonly used interbody spacer devices for ACDF. Although studies have been conducted to compare the efficacies of these two interbody materials, the question remains regarding the superiority of one over the other. Therefore, the authors conducted a systematic review and meta-analysis to compare nonunion, subsidence, and reoperation rates after ACDF using allograft and PEEK cages as interbody devices. METHODS: In this systematic review and meta-analysis, the authors systematically searched the MEDLINE, EMBASE, and Cochrane Library databases for studies published prior to November 2023 that compared the efficacy and safety of allograft and PEEK cages for ACDF. A pooled analysis was designed to identify differences in nonunion, subsidence, and reoperation rates between the two interbody devices. RESULTS: Ten studies involving 1462 patients (allograft, 852 patients; PEEK cage, 610 patients) were included. The pooled analysis demonstrated that allograft had a significantly lower rate of nonunion compared to that of PEEK cages (OR 0.33, 95% CI 0.14-0.79; p = 0.01). Furthermore, the reoperation rate due to nonunion was significantly higher with PEEK cages compared to that with allograft (OR 0.28, 95% CI 0.11-0.71; p < 0.01), whereas the reoperation rate due to overall causes did not display significant results (OR 0.38, 95% CI 0.11-1.29; p = 0.12). The incidence of significant subsidence (OR 0.66, 95% CI 0.28-1.55; p = 0.34) and the mean amount of subsidence (standard mean difference 0.03, 95% CI -0.42 to 0.47; p = 0.90) did not demonstrate significant differences between allograft and PEEK cages. CONCLUSIONS: Overall, the current meta-analysis suggests the advantages of allograft over PEEK cages used for ACDF, due to an enhanced fusion rate and minimized revision risk, with no increase in the risk of subsidence.

Does Spinal Cord-Canal Mismatch Adversely Affect the Clinical Outcomes of Anterior Cervical Discectomy and Fusion for the Treatment of Cervical Myelopathy?

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To clarify whether clinical outcomes of anterior cervical discectomy and fusion (ACDF), is affected by presence of spinal canal-cord mismatch (SCCM). SUMMARY OF BACKGROUND DATA: SCCM is considered a factor that would moderately influence surgeons to perform posterior surgery since it could widen the spinal canal, while an anterior approach could only remove degenerative pathologies grown into the spinal canal. METHODS: We retrospectively reviewed 186 patients who underwent ACDF and had been followed-up for >2 years. Patients with spinal cord occupation ratio (SCOR) of ≥0.7 were classified into the SCCM group, while those with a SCOR of <0.7 were included in the no-SCCM group. Patient demographics, cervical sagittal parameters, neck pain visual analog scale (VAS), arm pain VAS, and Japanese Orthopedic Association (JOA) score were assessed. JOA score was the primary outcome of the study. RESULTS: One-hundred and forty-seven patients (79.0%) were included into the no-SCCM group, while 39 patients (21.0%) were classified into the SCCM group. Postoperative radiographic parameters including C2-C7 lordosis, C2-C7 sagittal vertical axis, and range of motion did not significantly differ between the two groups. Neck pain VAS, arm pain VAS, and JOA score (no-SCCM group, from 13.7±2.5 to 14.6±2.3, P<0.001; SCCM group, from 13.8±1.6 to 15.0±2.0, P<0.001) significantly improved after the operation in both groups, and results were not significantly different between the two groups. Furthermore, SCOR was not significantly associated with JOA recovery rate at 2 years postoperatively in linear regression analysis. CONCLUSION: Clinical and radiographic outcomes of ACDF were not affected by the presence of SCCM. Furthermore, SCOR was not significantly associated with neurologic recovery at 2 years of follow-up. Therefore, ACDF can be safely and effectively applied for treating cervical myelopathy, regardless of the presence of SCCM, when other factors favor the anterior approach. LEVEL OF EVIDENCE: 3.

Biomedical Device Surface Treatment by Laser-Driven Hydroxyapatite Penetration-Synthesis Technique for Gapless PEEK-to-Bone Integration.

Polyetheretherketone (PEEK), a bioinert polymer known for its mechanical properties similar to bone, is capable of averting stress shielding. Due to these attributes, it finds applications in diverse fields like orthopedics, encompassing cervical disc replacement for the neck and spine, along with dentistry and plastic surgery. However, due to insufficient bonding with bone, various methods such as hydroxyapatite (HA) coating on the surface are attempted. Nonetheless, the interface between the polymer and ceramic, two different materials, tended to delaminate after transplantation, posing challenges in preventing implant escape or dislodgement. This research delves into the laser-driven hydroxyapatite penetration-synthesis technique. Differing from conventional coating methods that bond layers of dissimilar materials like HA and PEEK, this technology focuses on synthesizing and infiltrating ionized HA within the PEEK substrate resulting in an interface-free HA-PEEK surface. Conversely, HA-PEEK with this technology applied achieves complete, gap-free direct bone-implant integration.  Our research involved the analysis of various aspects. By means of these, we quantitatively assesed the enhanced bone bonding characteristics of HA-PEEK surfaces treated with this approach and offered and explanation for the mechanism responsible for direct bone integration.

Machine Learning-Based Etiologic Subtyping of Ischemic Stroke Using Circulating Exosomal microRNAs.

Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study explored the utility of circulating microRNAs encapsulated in extracellular vesicles (EV-miRNAs) to distinguish the following ischemic stroke subtypes: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and small artery occlusion (SAO). Using next-generation sequencing (NGS) and machine-learning techniques, we identified differentially expressed miRNAs (DEMs) associated with each subtype. Through patient selection and diagnostic evaluation, a cohort of 70 patients with acute ischemic stroke was classified: 24 in the LAA group, 24 in the SAO group, and 22 in the CES group. Our findings revealed distinct EV-miRNA profiles among the groups, suggesting their potential as diagnostic markers. Machine-learning models, particularly logistic regression models, exhibited a high diagnostic accuracy of 92% for subtype discrimination. The collective influence of multiple miRNAs was more crucial than that of individual miRNAs. Additionally, bioinformatics analyses have elucidated the functional implications of DEMs in stroke pathophysiology, offering insights into the underlying mechanisms. Despite limitations like sample size constraints and retrospective design, our study underscores the promise of EV-miRNAs coupled with machine learning for ischemic stroke subtype classification. Further investigations are warranted to validate the clinical utility of the identified EV-miRNA biomarkers in stroke patients.

Risk of Ischemic Stroke in Relation to Helicobacter pylori Infection and Eradication Status: A Large-Scale Prospective Observational Cohort Study.

Background/Aims: : A few studies have suggested the association between Helicobacter pylori (HP) infection and ischemic stroke. However, the impact of HP eradication on stroke risk has not been well evaluated. This study aimed to assess the influence of HP eradication on the incidence of ischemic stroke, considering the potential effect of sex. Methods: : This prospective observational cohort study was conducted at Seoul National University Bundang Hospital, from May 2003 to February 2023, and involved gastroscopy-based HP testing. Propensity score (PS) matching was employed to ensure balanced groups by matching patients in the HP eradicated group (n=2,803) in a 3:1 ratio with patients in the HP non-eradicated group (n=960). Cox proportional hazard regression analysis was used to evaluate the risk of ischemic stroke. Results: : Among 6,664 patients, multivariate analysis after PS matching indicated that HP eradication did not significantly alter the risk of ischemic stroke (hazard ratio, 0.531; 95% confidence interval, 0.221 to 1.270; p=0.157). Sex-specific subgroup analyses, both univariate and multivariate, did not yield statistically significant differences. However, Kaplan-Meier analysis revealed a potential trend: the females in the HP eradicated group exhibited a lower incidence of ischemic stroke than those in the HP non-eradicated group, although this did not reach statistical significance (p=0.057). Conclusions: : This finding suggests that HP eradication might not impact the risk of ischemic stroke. However, there was a trend showing that females potentially had a lower risk of ischemic stroke following HP eradication, though further investigation is required to establish definitive evidence.

The Perioperative Effects of Preoperative Radiotherapy in Metastatic Spinal Tumor Patients.

OBJECTIVE: Radiotherapy is one of the important treatment options for metastatic spinal tumors but is not the definite intervention in all cases, as there are patients who still require surgical treatment because of severe pain or neurologic events after this treatment. We evaluated the perioperative effects of preoperative radiotherapy in these cases as a future guide for surgeons on critical considerations in this period. METHODS: We included 328 patients in this study who had undergone decompression and fusion surgery for metastatic spinal tumors. Patients who underwent surgery with preoperative radiotherapy were designated as the radiotherapy group (group RT, n = 81), and cases of surgery without preoperative radiotherapy were assigned to the non-radiotherapy group (group nRT, n = 247). We compared the demographic, intraoperative, and postoperative factors between these 2 groups. RESULTS: In terms of intraoperative factors, statistically significant differences were evident in operation time, estimated blood loss, and transfusion (RT vs. nRT: 188.1 ± 80.7 minutes vs. 231.2 ± 106.1 minutes, 607.2 ± 532.7 mL vs. 830.1 ± 1324.7 mL, and 30.9% vs. 43.3%, P < 0.001, P < 0.031, and P < 0.048, respectively). With regard to postoperative factors, the incidence of infection, wound problems, and local recurrence were statistically higher in group RT (RT vs. nRT: 6.2% vs. 0.8%, 12.3% vs. 0.8%, 23.4% vs. 13.7%, P = 0.004, P < 0.001, and P = 0.038, respectively). CONCLUSIONS: Preoperative radiotherapy has the intraoperative advantages of reducing bleeding and shortening the operating time, but postoperative caution is needed because of the possibility of infection, wound problems, and local recurrence increases.

Differences in the risk of clinical failure between thiopurine and methotrexate in bio-naïve patients with Crohn's disease: a Korean nationwide population-based study.

Background: Although immunomodulators are widely prescribed in patients with Crohn's disease (CD), it is unclear whether there is a difference in treatment outcomes between thiopurines and methotrexate (MTX). Objective: To compare the risk of clinical failure between thiopurines and MTX in bio-naïve patients with CD. Design: Nationwide, population-based study. Methods: We used claims data from the Korean National Health Insurance Service. After inverse probability of treatment weighting, logistic regression and Cox proportional hazard analyses were used to evaluate the risk of clinical failure in bio-naïve patients with CD treated with thiopurine (thiopurine group) or MTX (MTX group). Results: Overall, 10,296 adult and pediatric patients with CD [9912 (96.3%) and 384 (3.7%) in the thiopurine and MTX groups, respectively] were included. The odds ratios (ORs) of failure to induce remission were significantly higher in the MTX group than in the thiopurine group [adjusted OR (aOR), 1.115; 95% confidence interval (CI), 1.045-1.190; p = 0.001]. However, the opposite result was observed only in patients without concomitant steroid use: the MTX group had a lower risk of induction failure than the thiopurine group (aOR, 0.740; 95% CI, 0.673-0.813; p < 0.001). The risk of overall maintenance failure was higher in the MTX group than in the thiopurine group [adjusted hazard ratio (aHR), 1.117; 95% CI, 1.047-1.191; p = 0.001]. The risk of overall maintenance failure was higher in the standard-dose MTX group than in the low-dose MTX group (aHR, 1.296; 95% CI, 1.134-1.480; p < 0.001). There was no significant difference in the risk of maintenance failure according to the administration route of MTX. Conclusion: Thiopurine is more effective than MTX in inducing and maintaining remission in bio-naïve patients with CD; however, the concomitant use of steroids influences inducing remission.

Differences in treatment efficacy between thiopurine and methotrexate in patients with Crohn's disease who were not treated with biologics Immunomodulators (IMMs) used in the treatment of Crohn's disease (CD) include medications such as thiopurine and methotrexate (MTX). Although IMMs are widely prescribed for patients with CD, it remains unclear whether treatment outcomes differ according to the specific types and dosages of IMMs and administration routes of MTX. In this study, we investigated the risk of treatment failure between thiopurines and MTX in CD patients not undergoing biologic treatment. Patients treated with MTX had a higher risk of maintenance failure than those treated with thiopurines. There was no difference in the risk of treatment failure according to the dosage of thiopurine. However, the risk of maintenance failure was higher in patients receiving standard-dose MTX than in those receiving low-dose MTX. There was no difference in the risk of maintenance failure according to the administration route of MTX. Our study enriches the knowledge regarding the treatment efficacy of thiopurines and MTX for patients with CD and may help clinicians develop appropriate treatment plans.

WFUMB Guideline/Guidance on Liver Multiparametric Ultrasound: Part 1. Update to 2018 Guidelines on Liver Ultrasound Elastography.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the WFUMB Liver Elastography Guidelines Update released in 2018 and provides new evidence on the role of ultrasound elastography in chronic liver disease. The recommendations in this update were made and graded using the Oxford classification, including level of evidence (LoE), grade of recommendation (GoR) and proportion of agreement (Oxford Centre for Evidence-Based Medicine [OCEBM] 2009). The guidelines are clinically oriented, and the role of shear wave elastography in both fibrosis staging and prognostication in different etiologies of liver disease is discussed, highlighting advantages and limitations. A comprehensive section is devoted to the assessment of portal hypertension, with specific recommendations for the interpretation of liver and spleen stiffness measurements in this setting.

Impact of Smoking and Alcohol Consumption on Early-Onset Gastric Cancer Development in Young Koreans: A Population-Based Study.

PURPOSE: Although smoking and alcohol consumption are known risk factors for gastric cancer (GC), studies assessing their effects on early-onset GC are limited. In this nationwide, population-based, prospective cohort study, we assessed the effects of smoking and alcohol consumption on early-onset GC in patients aged <50 years. MATERIALS AND METHODS: We analyzed data of patients aged 20-39 years who underwent cancer and general health screening in the Korean National Health Screening Program between 2009 and 2012. We calculated the adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for GC incidence until December 2020. RESULTS: We enrolled 6,793,699 individuals (men:women=4,077,292:2,716,407) in this cohort. The mean duration of follow-up was 9.4 years. During follow-up, 9,893 cases of GC (men:women=6,304:3,589) were reported. Compared with the aHRs (95% CI) of never-smokers, those of former and current-smokers were 1.121 (1.044-1.205) and 1.282 (1.212-1.355), respectively. Compared with the aHRs (95% CI) of non-consumers, those of low-moderate- and high-risk alcohol consumers were 1.095 (1.046-1.146) and 1.212 (1.113-1.321), respectively. GC risk was the highest in current-smokers and high-risk alcohol consumers (1.447 [1.297-1.615]). Interestingly, alcohol consumption and smoking additively increased the GC risk in men but not in women (Pinteraction=0.002). CONCLUSION: Smoking and alcohol consumption are significant risk factors for early-onset GC in young Koreans. Further studies are needed to investigate sex-based impact of alcohol consumption and smoking on GC incidence in young individuals.

Sex Difference in the Effect of Bifidobacterium longum on Repeated Water Avoidance Stress-induced Gut Dysbiosis in Wistar Rats.

Dysbiosis in gut microbiota is known to contribute to development of irritable bowel syndrome. We tried to investigate the effect of Bifidobacterium longum on repeated water avoidance stress (WAS) in a Wistar rat model. The three groups (no-stress, WAS, and WAS with B. longum) of rats were allocated to sham or WAS for 1 hour daily for 10 days, and B. longum was administered through gavage for 10 days. Fecal pellet numbers were counted at the end of each 1-hour session of WAS. After 10 days of repeated WAS, the rats were eutanized, and the feces were collected. WAS increased fecal pellet output (FPO) significantly in both sexes (P < 0.001), while the female B. longum group showed significantly decreased FPO (P = 0.005). However, there was no consistent change of myeloperoxidase activity and mRNA expression of interleukin-1ß and TNF-α. Mast cell infiltration at colonic submucosa increased in the female WAS group (P = 0.016). In terms of fecal microbiota, the repeated WAS groups in both sexes showed different beta-diversity compared to control and WAS with B. longum groups. WAS-induced mast cell infiltration was reduced by the administration of B. longum in female rats. Moreover, administration of B. longum relieved WAS-caused dysbiosis, especially in female rats. In conclusion, B. longum was beneficial for WAS-induced stress in rats, especially in females.

Does Preoperative Radiation Therapy Performed for Metastatic Spine Cancer at the Cervical Spine Increase Perioperative Complications of Anterior Cervical Surgery?

Background: Radiation therapy (RT) performed before anterior cervical spine surgery (ACSS) may cause fascial plane fibrosis, decreased soft-tissue vascularity, and vertebral body weakness, which could increase the risk of esophageal and major vessel injuries, wound complications, and construct subsidence. Therefore, this study aimed to evaluate whether preoperative RT performed for metastatic spine cancer (MSC) at the cervical spine increases perioperative morbidity for ACSS. Methods: Forty-nine patients who underwent ACSS for treatment of MSC at the cervical spine were retrospectively reviewed. All the patients underwent anterior cervical corpectomy via the anterior approach. Patient demographics, surgical factors, operative factors, and complications were recorded. Results of patients who were initially treated with RT before ACSS (RT group) were compared with those who did not receive RT before ACSS (non-RT group). Results: Eighteen patients (36.7%) were included in the RT group, while the remaining 31 (63.3%) were included in the non-RT group. Surgery-related factors, including operation time (p = 0.109), estimated blood loss (p = 0.246), amount of postoperative drainage (p = 0.604), number of levels operated (p = 0.207), and number of patients who underwent combined posterior fusion (p = 0.768), did not significantly differ between the 2 groups. Complication rates, including esophageal injury, dural tear, infection, wound dehiscence, and mechanical failure, did not significantly differ between the RT and non-RT groups. Early subsidence was significantly greater in the non-RT group compared to that in the RT group (p = 0.012). Conclusions: RT performed before surgery for MSC does not increase the risk of wound complication, mechanical failure, or vital structure injury during ACSS. The surgical procedural approach was not complicated by previous RT history. Therefore, surgeons can safely choose the anterior approach when the number of levels or location of MSC favors anterior surgery, and performing a posterior surgery is unnecessary due to a concern that previous RT may increase complication rates of ACSS.