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Background/aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acidrelated disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing., Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatmentemergent adverse events (TEAEs)., Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, -0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, -0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively., Conclusions: Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

We investigated an asymmetric slab grating structure to achieve significant tuning of the quality (Q) factor for a leaky mode while minimizing frequency variation. This structure comprises two identical gratings placed on the top and bottom of a slab waveguide, with one grating laterally shifted to introduce asymmetry. Simulations demonstrate that lateral shifting of one grating induces extensive changes in the Q-factor with minimal frequency variation, particularly near the band-flip filling fraction because the band-flip filling fraction remains unaffected by the shifting. The independence of the band-flip filling fraction from lateral shifting is attributed to the superposition property of Bragg scattering processes in the asymmetric grating structure. Experimental verification in the terahertz range confirms significant control over the Q-factor of the leaky mode of the structure. The proposed asymmetric slab grating structure offers possibilities for mechanically controllable optical devices, which are applicable to tunable filters and sensors. This study advances our understanding and application of leaky modes in asymmetric grating structures, revealing a previously unexplored aspect of asymmetric optical lattice., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

We used deep learning methods to develop an AI model capable of autonomously delineating cancerous regions in digital pathology images (H&E-stained images). By using a transgenic brain tumor model derived from the TS13-64 brain tumor cell line, we digitized a total of 187 H&E-stained images and annotated the cancerous regions in these images to compile a dataset. A deep learning approach was executed through DEEP:PHI, which abstracts Python coding complexities, thereby simplifying the execution of AI training protocols for users. By employing the Image Crop with Mask technique and patch generation method, we not only maintained an appropriate data class balance but also overcame the challenge of limited computing resources. This approach enabled us to successfully develop an AI training model that autonomously segments cancerous areas. This AI model enables the provision of guiding images for determining cancerous areas with minimal assistance from neuropathologists. In addition, the high-quality, large dataset curated for training using the proposed approach contributes to the development of novel terahertz imaging-based AI cancer diagnosis technologies and accelerates technological advancements., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: In lymphedema, the accumulation of subcutaneous interstitial fluid is the most characteristic feature. Bioimpedance analysis (BIA) is a promising technique to measure the amount of body components using a noninvasive method. In this study, we determined the clinical significance of BIA parameters in upper limb lymphedema with surgical treatment such as lymphovenous anastomosis or vascularized lymph node transfer. Methods and Results: A single-center retrospective study using a multifrequency BIA. Perioperative BIA parameters such as extracellular water ratio or fat-free mass (FFM) ratio and limb volume defined as percentage of excess volume (PEV) were measured. The relationships between the magnitude of change in PEV and BIA parameters during surgery were evaluated. Out of 48 unilateral lymphedema patients, 46 were female and the average age was 55.4 years. PEV and all BIA parameters showed a significant decrease after surgery ( p < 0.001). There were significant correlations between ΔPEV and the degree of changes in all BIA parameters. ΔFFM ratio showed the highest correlation with the amount of change in PEV ( r = 0.599, p < 0.001). Conclusion: BIA parameters correlated well with the volume change after surgery. BIA could be useful as a quick and easy tool for follow-up after lymphedema surgery.

Background/aims: Little is known about the practical clinical application of neuromodulators and psychiatric treatments in patients with functional gastrointestinal disorders (FGIDs). We investigate the knowledge, attitudes, and practices of Korean clinicians regarding the use of neuromodulators and psychiatric treatments for FGIDs., Methods: This prospective, online, cross-sectional study was conducted between May and August 2022. A questionnaire regarding the knowledge, attitude, and practice of neuromodulators and psychiatric treatments for FGIDs was developed and administered to primary care clinicians and gastroenterologists in university hospitals in Korea., Results: Overall, 451 clinicians from primary (n = 179, 39.7%), secondary (n = 113, 25.1%), and tertiary (n = 159, 35.3%) hospitals participated in the survey. Most of them considered that neuromodulators (98.7%) and psychiatric treatment (86.5%) were required for patients with FGIDs. However, approximately one-third of them did not prescribe neuromodulators, mainly due to unfamiliarity with the drugs, and only one-quarter considered psychiatric referral. Compared to gastroenterologists at university hospitals, primary care clinicians' prescriptions had a lower rate (87.2% vs 64.2%, P < 0.001) and shorter duration of neuromodulator. The psychiatric referral rate was lower for primary care clinicians than for gastroenterologists at university hospitals (19.0% vs 34.2%, P < 0.001)., Conclusions: Knowledge, attitude, and practice levels regarding neuromodulators and psychiatric treatment among clinicians are inhomogeneous, and a knowledge gap exists between primary care clinicians and gastroenterologists at university hospitals. Encouraging ongoing education for Korean clinicians regarding the appropriate use of neuromodulators and psychiatric treatments in patients with FGIDs is suggested.

Purpose: This study aims to explore the relationship between soy food consumption and gastric cancer (GC) risk, accounting for Helicobacter pylori infection status., Materials and Methods: We analyzed data from patients with GC and healthy individuals prospectively enrolled by 6 hospitals between 2016 and 2018. Dietary intake was evaluated using questionnaires that categorized seven dietary habits and 19 food groups. Multivariate logistic regression models were applied to examine associations. Model I adjusted for various epidemiological factors, while Model II included further adjustments for H. pylori infection. Primary exposures examined were consumption frequencies of nonfermented, unsalted soy foods (soybean/tofu) and fermented, salty soy foods (soybean paste stew)., Results: A total of 5,535 participants were included, with 1,629 diagnosed with GC. In Model I, the frequency of soybean/tofu consumption was inversely related to GC risk; adjusted odd ratios (aORs) were 0.62 (95% confidence interval [CI], 0.48-0.8), 0.38 (95% CI, 0.3-0.49), 0.42 (95% CI, 0.33-0.53), and 0.33 (95% CI, 0.27-0.42) for 1 time/week, 2 times/week, 3 times/week, and ≥4 times/week. Consumption of 2 servings/week of soybean paste stew showed the lowest GC association, forming a V-shaped curve. Both low (aOR, 4.03; 95% CI, 3.09-5.26) and high serving frequencies of soybean paste stew (aOR, 2.23; 95% CI, 1.76-2.82) were associated with GC. The association between soy foods and GC in Model II was similar to that in Model I. The soy food-GC associations were consistent across sexes in Model I. Nonetheless, the positive correlation between frequent consumption of soybean paste stew (≥5 times/week) and GC was more pronounced in women (aOR, 7.58; 95% CI, 3.20-17.99) compared to men (aOR, 3.03; 95% CI, 1.61-5.88) in Model II. Subgroup analyses by H. pylori status and salty diet revealed a consistent inverse relationship between soybean/tofu and GC risk. In contrast, soybean paste stew showed a V-shaped relationship in H. pylori -positive or salty diet groups and no significant association in the H. pylori -negative group., Conclusions: Soybean/tofu intake is consistently associated with a decreased risk of GC. However, the relationship between soybean paste stew consumption and GC risk varies, depending on H. pylori infection status and dietary salt intake., Trial Registration: ClinicalTrials.gov Identifier: NCT03046745., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2024. Korean Gastric Cancer Association.)

Background: The authors investigated postoperative nasal morphologic changes in patients undergoing secondary correction of cleft-lip nose with septal repositioning and alar cartilage suspension during preschool age., Methods: The authors performed a retrospective review of 77 patients who underwent secondary correction of cleft-lip nose. The patients were 5 to 6 years of age and underwent intermediate rhinoplasty by alar cartilage suspension, with or without septal repositioning. They were divided into 2 groups based on time, encompassing septal repositioning (September of 2015 through November of 2017) and control (November of 2009 through August of 2015) groups. The authors performed a photogrammetric comparison by assessing the postoperative nasal morphologic changes using linear and angular measures. The cleft-to-noncleft-side ratio of each parameter was measured for the nostril width and height, nostril area, and caudal septal deviation angle., Results: Among the 77 patients, 43 were selected as the septal repositioning group and 34 as the control group. Evaluation timing was 5.32 ± 0.45 years of age for the preoperative period (T0), 6.57 ± 0.5 years of age for short-term follow-up (T1), and 9.28 ± 0.65 years of age for long-term follow-up (T2). The septal repositioning group showed significantly improved nostril width ratio and caudal septal deviation angle in the T1 and T2 periods. Septal repositioning significantly decreased the nostril area ratio in the T1 and T2 periods due to decreased cleft-side and increased noncleft-side nostril area., Conclusion: The secondary correction of cleft-lip nose with septal repositioning during preschool age offers a second chance to correct nasal appearance by balancing the nostril symmetry and correcting the caudal septal deviation., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Many young microsurgeons begin their careers at established hospitals where microsurgery resources are limited. This article shares the authors' experiences in overcoming challenges and establishing a microsurgery practice in a new hospital. Due to the lack of equipment, limited support from colleagues, absence of discussion partners, fear of failure, and unpredictable situations, many aspiring microsurgeons lose their motivation. The purpose of this article is to guide future microsurgeons by describing the author's actions and suggesting improvements for their first free flap case. Key factors for building a successful, sustainable, and enjoyable microsurgery practice include remembering your training and mentors, acquiring fundamental knowledge of microsurgery, creating a supportive ecosystem, and having fun., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background/aims: Prokinetic agents and neuromodulators are among the treatment options for functional dyspepsia (FD), but their comparative efficacy is unclear. We aimed to compare the efficacy of mosapride controlled-release (CR) and nortriptyline in patients with FD after 4 weeks of treatment., Methods: Participants with FD were randomly assigned (1:1) to receive mosapride CR (mosapride CR 15 mg and nortriptyline placebo) or nortriptyline (mosapride CR placebo and nortriptyline 10 mg) in double-placebo, double-blinded, randomized controlled, parallel clinical study. The primary endpoint was defined as the proportion of patients with overall dyspepsia improvement after 4 weeks treatment. The secondary endpoints were changes in individual symptom scores, anxiety, depression, and quality of life., Results: One hundred nine participants were recruited and assessed for eligibility, and 54 in the mosapride CR group and 50 in the nortriptyline group were included in the modified intention-to-treat protocol. The rate of overall dyspepsia improvement was similar between groups (53.7% vs 54.0%, P = 0.976). There was no difference in the efficacy of mosapride CR and nortriptyline in a subgroup analysis by FD subtype (59.3% vs 52.5% in postprandial distress syndrome, P = 0.615; 44.4% vs 40.0% in epigastric pain syndrome, P = > 0.999; 50.0% vs 59.1% in overlap, P = 0.565; respectively). Both treatments significantly improved anxiety, depression, and quality of life from baseline., Conclusion: Mosapride CR and nortriptyline showed similar efficacy in patients with FD regardless of the subtype. Both treatments could be equally helpful for improving quality of life and psychological well-being while also relieving dyspepsia.

Sulfur, a critical element for bacterial growth, is not directly utilized by bifidobacteria, rendering the sulfur-containing amino acid biosynthesis pathway, particularly for cysteine and methionine, poorly understood. This research identifies six genes involved in this pathway through re-annotation of the Bifidobacterium longum DJO10A genome. These genes play crucial roles in bioconversion processes essential for cysteine utilization, highlighting its significance in sulfur metabolism. Our study uncovers a novel regulatory mechanism of these pathways under varying cysteine concentrations. We demonstrate a dual-pathway mechanism for methionine biosynthesis: one directly utilizing cysteine (trans-sulfurylation pathway) and another utilizing H 2 S derived from cysteine degradation (direct sulfurylation pathway). This regulatory dual-pathway mechanism is contingent on environmental cysteine levels, with both pathways activated at low cysteine levels, while higher levels predominantly engage the H 2 S-utilizing pathway. This investigation not only advances our understanding of DJO10A's metabolic capabilities but also underscores the bacterium's adaptability through sophisticated regulatory mechanisms for sulfur-containing amino acid biosynthesis. The elucidation of these pathways provides valuable insights into the survival strategies of bifidobacteria in the gut environment, where sulfur sources can vary greatly. Through detailed genomic, transcriptional, and enzymatic analyses, this study significantly contributes to the field of microbiology, offering a foundation for future research on gut microbiota metabolic pathways and their implications for host health.

In a global context, bacterial diseases caused by pathogenic bacteria have inflicted sustained damage on both humans and animals. Although antibiotics initially appeared to offer an easy treatment for most bacterial infections, the recent rise of multidrug-resistant bacteria, stemming from antibiotic misuse, has prompted regulatory measures to control antibiotic usage. Consequently, various alternatives to antibiotics are being explored, with a particular focus on bacteriophage (phage) therapy for treating bacterial diseases in animals. Animals are broadly categorized into livestock, closely associated with human dietary habits, and companion animals, which have attracted increasing attention. This study highlights phage therapy cases targeting prominent bacterial strains in various animals. In recent years, research on bacteriophages has gained considerable attention, suggesting a promising avenue for developing alternative substances to antibiotics, particularly crucial for addressing challenging bacterial diseases in the future., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2024 Korean Society of Animal Science and Technology.)

Purpose: The Armed Forces Trauma Center of Korea was established in April 2022. This study was conducted to report our 1-year experience of treating soldiers with open fractures of the lower extremity., Methods: In this case series, we reviewed the medical records of 51 Korean soldiers with open fractures of the lower extremity between April 2022 and March 2023 at a trauma center. We analyzed patients with Gustilo-Anderson type II and III fractures and reported the duration of transportation, injury mechanisms, injured sites, and associated injuries. We also presented laboratory findings, surgery types, intensive care unit stays, hospital stays, rehabilitation results, and reasons for psychiatric consultation. Additionally, we described patients' mode of transport., Results: This study enrolled nine male patients who were between 21 and 26 years old. Six patients had type II and three had type III fractures. Transport from the accident scene to the emergency room ranged from 75 to 455 minutes, and from the emergency room to the operating room ranged from 35 to 200 minutes. Injury mechanisms included gunshot wounds, landmine explosions, grenade explosions, and entrapment by ship mooring ropes. One case had serious associated injuries (inhalation burn, open facial bone fractures, and hemopneumothorax). No cases with serious blood loss or coagulopathies were found, but most cases had a significant elevation of creatinine kinase. Two patients underwent vascular reconstruction, whereas four patients received flap surgery. After rehabilitation, six patients could walk, one patient could move their joints actively, and two patients performed active assistive movement. Eight patients were referred to the psychiatry department due to suicidal attempts and posttraumatic stress disorder., Conclusions: This study provides insights into how to improve treatment for patients with military trauma, as well as medical services such as the transport system, by revising treatment protocols and systematizing treatment., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (© 2023 The Korean Society of Traumatology.)

Background/aims: Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that typically requires long-term maintenance therapy. However, little is known about patient preferences and satisfaction and real-world prescription patterns regarding maintenance therapy for GERD., Methods: This observational, cross-sectional, multicenter study involved patients from 18 referral hospitals in Korea. We surveyed patients who had been prescribed proton pump inhibitors (PPIs) for GERD for at least 90 days with a minimum follow-up duration of 1 year. The main outcome was overall patient satisfaction with different maintenance therapy modalities., Results: A total of 197 patients were enrolled. Overall patient satisfaction, patient preferences, and GERD health-related quality of life scores did not significantly differ among the maintenance therapy modality groups. However, the on-demand therapy group experienced a significantly longer disease duration than the continuous therapy group. The continuous therapy group demonstrated a lower level of awareness of potential adverse effects associated with PPIs than the on-demand therapy group but received higher doses of PPIs than the on-demand therapy group. The prescribed doses of PPIs also varied based on the phenotype of GERD, with higher doses prescribed for non-erosive reflux disease than erosive reflux disease., Conclusion: Although overall patient satisfaction did not significantly differ among the different PPI maintenance therapy modality groups, awareness of potential adverse effects was significantly different between the on-demand and continuous therapy groups.

Background/aims: It remains unclear which maintenance treatment modality is most appropriate for mild gastroesophageal reflux disease (GERD). We aimed to compare on-demand treatment with continuous treatment using a proton pump inhibitor (PPI) in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis., Methods: Patients whose GERD symptoms improved after 4 weeks of standard dose PPI treatment were prospectively enrolled at 25 hospitals. Subsequently, the enrolled patients were randomly assigned to either an on-demand or a continuous maintenance treatment group, and followed in an 8-week interval for up to 24 weeks., Results: A total of 304 patients were randomized to maintenance treatment (continuous, n = 151 vs on-demand, n = 153). The primary outcome, the overall proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the non-inferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%). Compared with the on-demand group, the GERD symptom and health-related quality of life scores significantly more improved and the overall satisfaction score was significantly higher in the continuous treatment group, particularly at week 8 and week 16 of maintenance treatment. Work impairment scores were not different in the 2 groups, but the prescription cost was less in the on-demand group. Serum gastrin levels significantly elevated in the continuous treatment group, but not in the on-demand group., Conclusions: Continuous treatment seems to be more appropriate for the initial maintenance treatment of non-erosive GERD or mild erosive esophagitis than on-demand treatment. Stepping down to on-demand treatment needs to be considered after a sufficient period of continuous treatment.

Background  This is a prospective study on 118 patients who underwent lymphaticovenous anastomosis (LVA) due to secondary lower limb lymphedema between January 2018 and October 2020 to evaluate patients' quality of life (QOL) using the Quality of Life Measure for Limb Lymphedema (LYMQoL) questionnaire. Methods  The outcome measurement included the LYMQoL leg scoring system tool evaluating the function, appearance, symptom, mood, and overall outcome. In addition, correlation analysis was performed for three factors: based on International Society of Lymphology (ISL) stages, disease duration, and amount of volume reduction. Results  The LYMQoL tool overall satisfaction score significantly increased at all intervals from 4.4 ± 0.2 preoperative to 6.5 ± 0.3 postoperative at 12 months ( p  < 0.001). Significant findings were seen for each domain scores compared preoperatively and at 12 months: function score (18.6 ± 0.5 to 15.4 ± 0.6), appearance score (17.8 ± 0.5 to 16.0 ± 0.6), symptom score (11.8 ± 0.3 to 8.9 ± 0.4), and mood score (14.5 ± 0.4 to 11.4 ± 0.5; p  < 0.05). The correlation analysis between improvement of the overall score and the ISL stage ( p  = 0.610, correlation coefficient [ r ] = - 0.047), disease duration ( p  = 0.659, r  = - 0.041), and amount of limb volume reduction ( p  = 0.454, r  = - 0.070) showed no statistical significance. Conclusion  The QOL of secondary lower limb lymphedema patients was significantly improved after LVA regardless of the severity of disease, duration of disease, and amount of volume reduction after LVA. Understanding the patient-reported outcome measurement will help the surgeons to manage and guide the expectations of the patients., Competing Interests: Conflict of Interest H.P.S. is an editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Background/aims: Increasing resistance to clarithromycin (CAM) of Helicobacter pylori ( H. pylori ) is one of the main causes of recent decrease in eradication rate of standard triple therapy. The aim of this study was to evaluate the usefulness of 7-day tailored therapy based on the existence of CAM resistance., Methods: From January 2017 to May 2022, a total of 481 consecutive patients with H. pylori infection were recruited in Daegu Catholic University Medical Center. Treatment regimen was selected based on the result of CAM resistance test. Patients with CAM resistance (R group) were treated with bismuth-based quadruple therapy for 7 days. Patients without CAM resistance (S group) were treated with standard triple therapy for 7 days., Results: The overall H. pylori eradication rate was 89.4% (379 of 424) by per-protocol (PP) analysis. Patients with CAM resistance mutation included 166 patients (34.5%). The eradication rates of each group were 88.8% (135 of 152) and 89.7% (244 of 272) by PP analysis, for R and S group respectively. By intention-to-treat (ITT) analysis, the eradication rates were 81.3% (135 of 166) and 77.5% (244 of 315) for R and S group. CAM resistance was identified with a dual-priming oligonucleotide-based multiplex PCR., Conclusions: In spite of this high CAM resistance (34.5%), the eradication rate of 7-day tailored therapy based on the existence of CAM resistance was 89.4%. The 7-day tailored therapy based on CAM resistance could be an acceptable treatment selection strategy for H. pylori eradication.

Detecting and identifying the origins of foodborne pathogen outbreaks is a challenging. The Next-Generation Sequencing (NGS) panel method offers a potential solution by enabling efficient screening and identification of various bacteria in one reaction. In this study, new NGS panel primer sets that target 18 specific virulence factor genes from six target pathogens ( Bacillus cereus , Yersinia enterocolitica , Staphylococcus aureus , Vibrio cholerae , Vibrio parahaemolyticus , and Vibrio vulnificus ) were developed and optimized. The primer sets were validated for specificity and selectivity through singleplex PCR, confirming the expected amplicon size. Crosscheck and multiplex PCR showed no interference in the primer set or pathogenic DNA mixture. The NGS panel analysis of spiked water samples detected all 18 target genes in a single reaction, with pathogen concentrations ranging from 10 8 to 10 5 colony-forming units (CFUs) per target pathogen. Notably, the total sequence read counts from the virulence factor genes showed a positive association with the CFUs per target pathogen. However, the method exhibited relatively low sensitivity and occasional false positive results at low pathogen concentrations of 10 5 CFUs. To validate the detection and identification results, two sets of quantitative real-time PCR (qPCR) analyses were independently performed on the same spiked water samples, yielding almost the same efficiency and specificity compared to the NGS panel analysis. Comparative statistical analysis and Spearman correlation analysis further supported the similarity of the results by showing a negative association between the NGS panel sequence read counts and qPCR cycle threshold (Ct) values. To enhance NGS panel analysis for better detection, optimization of primer sets and real-time NGS sequencing technology are essential. Nonetheless, this study provides valuable insights into applying NGS panel analysis for multiple foodborne pathogen detection, emphasizing its potential in ensuring food safety., Competing Interests: E-SH, BK, IC, JC, and JP were employed by Sanigen Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Park, Kwon, Ha, Kang, Choi, Kwak, Choi, Lee, Kim, Kim, Park and Lee.)

Patients frequently report that stress causes or exacerbates gastrointestinal (GI) symptoms, indicating a functional relationship between the brain and the GI tract. The brain and GI tract are closely related embryologically and functionally, interacting in various ways. The concept of the brain-gut axis was originally established in the 19th and early 20th centuries based on physiological observations and experiments conducted in animals and humans. In recent years, with the growing recognition that gut microbiota plays a vital role in human health and disease, this concept has been expanded to the brain-gut-microbiota axis. The brain influences the motility, secretion, and immunity of the GI tract, with consequent effects on the composition and function of the gut microbiota. On the other hand, gut microbiota plays an essential role in the development and function of the brain and enteric nervous system. Although knowledge of the mechanisms through which the gut microbiota influences distant brain function is incomplete, studies have demonstrated communication between these organs through the neuronal, immune, and endocrine systems. The brain-gut-microbiota axis is an essential aspect of the pathophysiology of functional GI disorders such as irritable bowel syndrome, and is also involved in other GI diseases, including inflammatory bowel disease. This review summarizes the evolving concept of the brain-gut-microbiota axis and its implications for GI diseases, providing clinicians with new knowledge to apply in clinical practice.

Background:  In lymphedema, lymphatic fluid accumulates in the interstitial space, and localized swelling appears. Lymphovenous anastomosis (LVA) is the most widely used surgery to rebuild a damaged lymphatic system; however, assessing outcome of LVA involves performing volume measurements, which provides limited information on body composition changes. Therefore, we analyzed the bioelectrical impedance analysis (BIA) parameters that can reflect the status of lymphedema patients who underwent LVA., Methods:  We retrospectively reviewed records of 42 patients with unilateral lower extremity lymphedema who had LVA. We measured the perioperative BIA parameters such as extracellular water (ECW) ratio and volume as defined by the percentage of excess volume (PEV). We evaluated the relationship between the amount of change in PEV and in BIA parameters before and after surgery. We confirmed the correlation between ΔPEV and BIA parameters using Spearman's correlation., Results:  Most patients included had secondary lymphedema due to cancer. Average age was 51.76 years and average body mass index was 23.27. PEV and all BIA parameters after surgery showed a significant difference ( p  < 0.01) compared with preoperative measurements. The ECW ratio aff / unaff showed the strongest correlation with PEV with a correlation coefficient of 0.473 ( p  < 0.01)., Conclusion:  Our findings suggest that BIA parameters, especially ECW ratio aff / unaff could reflect the status of patients with lower limb lymphedema after LVA. Appropriate use of BIA parameters may be useful in the postoperative surveillance of patients., Competing Interests: None declared., (Thieme. All rights reserved.)

Background:  Elevation in different layers achieving thin flaps are becoming relatively common practice for perforator flaps. Although postreconstruction debulking achieves pleasing aesthetic results and is widely practiced, customized approach during elevation to achieve the ideal thickness will increase efficiency while achieving the best possible aesthetic outcome. Multiple planes for elevation have been reported along with different techniques but it is quite confusing and may lack correspondence to the innate anatomy of the skin and subcutaneous tissue., Methods:  This article reviews the different planes of elevation and aims to clarify the definition and classification in accordance to anatomy and present the pros and cons of elevation based on the different layers and provide technical tips for elevation., Results:  Five different planes of elevation for perforator flaps are identified: subfascial, suprafacial, superthin, ultrathin, and subdermal (pure skin) layers based on experience, literature, and anatomy., Conclusion:  These planes all have their unique properties and challenges. Understanding the benefits and limits along with the technical aspect will allow the surgeon to better apply the perforator flaps., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the K + /H + -ATPase enzyme in proton pumps within gastric parietal cells. Fexuprazan's suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner., Aim: To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE)., Methods: Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate of EE at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were compared between the groups., Results: Of the 263 randomized, 218 completed the study per protocol (fexuprazan 40 mg, n = 107; esomeprazole 40 mg, n = 111). Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8 [99.1% (106/107) vs 99.1% (110/111)]. There were no between-group differences in the EE healing rate at week 4 [90.3% (93/103) vs 88.5% (92/104)], symptom responses, and quality of life assessments. Additionally, serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups., Conclusion: Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8. We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE., Competing Interests: Conflict-of-interest statement: The corresponding author, Lee OY, had been a member of outside directors at the Daewoong Pharmaceutical Co., Ltd, form the period March 24 2018 to Nov 2 2021. All other authors declare no conflict of interests regarding this study., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The purpose of this retrospective study was to describe, evaluate, and compare the outcome between end-to-end and side-to-end lymphaticovenous anastomoses for all stages of lymphedema., Methods: A total of 123 patients were divided into the end-to-end ( n = 63) or the side-to-end ( n = 60) group. The demographics and intraoperative and postoperative findings were evaluated. In addition, subcategory evaluation was performed for early- and advanced-phase lymphedema., Results: The demographic findings were insignificant. The intraoperative findings showed a significantly higher number of lymphaticovenous anastomoses performed for the end-to-end group (4.1 ± 1.7) over the side-to-end group (3.2 ± 1.2) ( p < 0.001), whereas the number of different lymphatic vessels used per patient was not significant (3.4 ± 1.4 versus 3.2 ± 1.2; p = 0.386). The diameter of the lymphatic vessels was not significant (0.43 ± 0.06 mm versus 0.45 ± 0.09 mm; p = 0.136). Although both groups showed significant postoperative volume reduction, the side-to-end group had a significantly better reduction in all time intervals ( p < 0.03) and longitudinal outcome ( p = 0.004). However, the subcategory evaluation for early-phase patients showed no difference between the two groups, but a significantly better volume reduction ratio was noted for the side-to-end group at all time intervals ( p < 0.025) in addition to overall longitudinal outcome ( p = 0.004) in advanced lymphedema patients., Conclusions: This is the first study to report the efficacy of end-to-end versus side-to-end lymphaticovenous anastomosis in different phases of lymphedema. Although both end-to-end and side-to-end lymphaticovenous anastomoses are significantly effective in volume reduction, there was a significantly better reduction for the side-to-end group in advanced-phase lymphedema patients with stage II late and stage III disease, whereas no difference was noted for early-phase lymphedema patients., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Since the first food-borne outbreak of Salmonella enterica serovar Bareilly in the UK (2010), it has been recognized as a new type of food-borne pathogen in S. enterica. To detect and characterize this new serovar pathogen in South Korea, a total of 175 Salmonella strains was isolated and 31 isolates were identified as S. Bareilly from various food-borne outbreaks between 2014 and 2018. While pulsed-field gel electrophoresis (PFGE) analysis using Xba I revealed two major groups (A and B) each with two subgroups (A1, A2/B1, B2), average nucleotide identity (ANI), single nucleotide polymorphism (SNP), and in silico multilocus sequence typing (MLST) analyses confirmed only two major groups. Interestingly, extended SNP analysis with 67 S. Bareilly strains from outbreaks in other countries revealed that A group strains between 2014 and 2016 shared a close evolutionary relationship with the strains from outside of South Korea; however, the B group strains in 2018 were located in a separate SNP tree branch. These findings suggest that the A group may share common ancestor with the strains of previous outbreaks in the UK or other countries, while the B group is a new genotype. Comparative virulence factor (VF) analysis between the A and B group strains showed that S. Bareilly in the B group has more various than that of the A group. A comparative biofilm formation assay supports for this, which B group strain GG-21 has higher biofilm formation activity than A group strain GG-07. Antibiotic susceptibility test of 31 S. Bareilly strains revealed high susceptibility to 17 tested antibiotics, suggesting that S. Bareilly can be easily treated by antibiotics., Competing Interests: Author HN was employed by Sanigen Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Park, Kwon, Na, Lee, Lee and Ryu.)

Sourdough bread fermented with yeast and lactic acid bacteria (LAB) is thought to have various beneficial health effects. However, its beneficial effects were not fully evaluated with in vivo mouse model. To evaluate these effects in vivo , a mouse feeding study and microbiome analysis of white bread containing 40% sourdough (WBS) and yeast-leavened white bread (WB) were performed. Although feed consumption and body weight increased with WBS, the glycemic index was reduced, suggesting a diabetes-lowering effect, probably due to the presence of dietary fiber and short-chain fatty acids (SCFA). In addition, a mineral absorption test showed that WBS increased magnesium absorption owing to phytate degradation during fermentation. Interestingly, WBS decreased total cholesterol and triglycerides, probably due to the dietary fiber and SCFA in LAB. In addition, the ratio of low- and high-density lipoprotein was decreased in WBS, implying potential risk reduction for cardiovascular disease. An immunomodulatory assay of WBS revealed that pro-inflammatory cytokines TNF-α and IL-6 were decreased, suggesting anti-inflammatory activity. Gluten degradation by fermentation and antioxidation activity of menaquinol/ubiquinol by gut microbiota also supported the anti-inflammatory activity of sourdough bread. Furthermore, some beneficial gut bacteria, including Akkermansia , Bifidobacterium , and Lactobacillus , were increased in WBS. In particular, Akkermansia has been associated with anti-inflammatory properties. Consequently, WBS has beneficial effects on health, including decreased glycemic index and cholesterol, increased mineral availability and absorption, anti-inflammatory properties, and establishment of healthy gut microbiota., Competing Interests: Authors GK, DL, and DK were employed by SPC Research Institute of Food and Biotechnology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kwon, Park, Kwak, Cho, Kim, Lee, Kim, Kim and Lee.)

Complete genome sequence analysis of Bifidobacterium longum subsp. longum BCBL-583 isolated from a Korean female fecal sample showed no virulence factor or antibiotic resistance gene, suggesting human safety. In addition, this strain has oxygen and heat tolerance genes for food processing, and cholesterol reduction and mucin adhesion-related genes were also found. For in vivo evaluations, a high fat diet (HFD) mouse model was used, showing that BCBL-583 administration to the model (HFD-583) reduced the total cholesterol and LDL-cholesterol in the blood and decreased pro-inflammatory cytokines but increased anti-inflammatory cytokines, substantiating its cholesterol reduction and anti-inflammation activities. Subsequent microbiome analysis of the fecal samples from the HFD mouse model revealed that BCBL-583 administration changed the composition of gut microbiota. After 9 weeks feeding of bifidobacteria, Firmicutes, Actinobacteria, and Bacteroidetes increased, but Proteobacteria maintained in the HFD mouse models. Further comparative species-level compositional analysis revealed the inhibitions of cholesterol reduction-related Eubacterium coprostanoligenes and obesity-related Lactococcus by the supplementation of B. longum BCBL-583, suggesting its possible cholesterol reduction and anti-obesity activities. The correlation analysis of HFD-583 between the gut microbiota compositional change and cholesterol/immune response showed that Verrucomicrobia, Firmicutes, Actinobacteria, and Bacteroidetes may play an important role in cholesterol reduction and anti-inflammation. However, correlation analysis of Proteobacteria showed the reverse correlation in HFD-583. Interestingly, the correlation analysis of B. longum ATCC 15707 administration to HFD model showed similar patterns of cholesterol but different in immune response patterns. Therefore, this correlation analysis suggests that the microbial composition and inflammatory cytokine/total-cholesterol may be closely related in the administration of BCBL-583 in the HFD mice group. Consequently, BCBL-583 could be a good probiotic strain for gut health promotion through gut microbiota modulation., Competing Interests: C-HK and Y-SS were employed by Food Research Center, Binggrae Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kim, Kim, Kwon, Cho, Shin, Kim and Lee.)

Background: This retrospective case series compares the outcomes and postoperative oxygen levels in patients who underwent free flap versus primary closure/local flap reconstruction for ischemic diabetic foot wounds to determine the influence of free flap on the surrounding ischemic tissues. The authors hypothesized that the free flap would benefit the surrounding ischemic tissue as a nutrient flap by increasing the tissue oxygen content., Methods: The patients were divided into two groups: group 1 underwent free flap reconstruction, and group 2 underwent partial foot amputation with primary closure/local flap. Patient demographics, endovascular intervention, surgical outcome, postreconstruction intervention, and prereconstruction and postreconstruction transcutaneous oximetry were analyzed., Results: Among 54 patients, 36 were in group 1 and 18 were in group 2. There were no differences in patient demographics between the two groups. All patients had successful angioplasty. Statistical significance was noted in postreconstruction intervention in which group 2 required 2.8 ± 2.9 débridements (versus 1.2 ± 2.5 for group 1) and seven of 18 below-knee amputations (versus three of 36 for group 1) (p < 0.05). Transcutaneous partial pressure of oxygen levels were significantly higher in group 1 at 6 months after reconstruction (61.6 ± 7.5 versus 32.6 ± 5.8 mmHg) (p < 0.01)., Conclusion: This study shows that the role of the free flap in ischemic diabetic limb may expand beyond that of providing coverage over the vital structures, and it supports the use of the free flap as a nutrient to increase oxygen content in the ischemic diabetic foot., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: To perform head and neck reconstruction, the exact location of recipient vessels must be evaluated preoperatively. This study aimed to superimpose arterial and venous pathways identified by computed tomography angiography (CTA) on patients using augmented reality (AR) techniques to freely select recipient vessels., Methods: Patients who underwent reconstructive microsurgery due to defects on the scalp, forehead, and glabella from July 2019 to October 2019 were enrolled. The superficial temporal artery (STA) and superficial temporal vein (STV) were marked using hand-held Doppler. Furthermore, the three-dimensional reconstructed CTA image was superimposed on the patient's face using a smartphone application, Camera-Lucida, and marked. The accuracy of mapping was evaluated intraoperatively. Success rates and the time consumed for mapping were compared., Results: Twelve patients underwent preoperative marking. Success rates of STA mapping using the AR technology and hand-held Doppler were 100% and 83%, respectively (P = 0.48). The mean time consumed for STA marking was 90.2 ± 17.7 seconds and 121.0 ± 117.7 seconds, respectively (P  = 0.75). The success rate of STY marking with the AR technology was superior to that with hand-held Doppler (100% versus 58.3%; P = 0.037). STY marking was faster with the AR technology than with hand-held Doppler (mean time, 91.2 ± 25.7 seconds versus 94.5 ± 101.6 seconds; P = 0.007)., Conclusions: The AR technology could be the paradigm shift in the field of microsurgical reconstruction. it can connect threedimensional CTA data with patient topography, leading to not only more precise operations but also improved outcomes in patients undergoing microsurgical reconstruction., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Background/aims: Non-celiac gluten sensitivity is characterized by intestinal and extra intestinal symptoms associated with the consumption of gluten-containing food. Since biomarkers for non-celiac gluten sensitivity are lacking, its prevalence is estimated based on self-reported symptoms. However, no data exist on self-reported non-celiac gluten sensitivity in the Korean population. Thus, we aim to investigate the prevalence of self-reported non-celiac gluten sensitivity in the Korean population and to determine its demographic and clinical characteristics., Methods: This study surveyed Korean participants aged 18-80 years who visited gastroenterology outpatient clinics at 9 tertiary hospitals in South Korea from January 2016 to February 2017. They were questioned regarding symptoms related to gluten ingestion: degree of discomfort (visual analog scale score), frequency, time of symptom onset, and duration. Abdominal discomfort caused by 11 different kinds of gluten-containing Korean food items was investigated., Results: More non-celiac gluten sensitivity self-reporters were identified among those with irritable bowel syndrome (33.6%) than among controls (5.8%). Major gastrointestinal symptoms included bloating (75.0%), abdominal discomfort (71.3%), and belching (45.0%). Common extra-intestinal symptoms included fatigue (20.0%) and headache (13.7%). More than half of those who self-reported non-celiac gluten sensitivity (66.3%) developed symptoms within 1 hour of food ingestion, and symptoms were localized in the upper abdomen (37.5%) and entire abdomen (30.0%)., Conclusion: Our findings suggest that if there are gluten-related symptoms in irritable bowel syndrome, the possibility of accompanying non-celiac gluten sensitivity should be considered.

Background: Perforator flaps have revolutionized lower limb reconstruction by offering single-stage thin, pliable coverage with an excellent aesthetic match. Although anastomosis of the flap to a major artery remains the gold standard, perforator-to-perforator anastomosis has several advantages, including expedient recipient dissection and increased recipient options in vessel-depleted extremities. The aim of this study was to compare flap survival when a perforator or major artery was used as a recipient vessel., Methods: A retrospective cohort of free perforator flaps for lower limb reconstruction was reviewed. Demographics, comorbidities, vascular status, defect characteristics, operative details, and complications were recorded. Outcomes for perforator and major artery recipients were compared., Results: Four hundred twenty-three flaps were performed for various reasons using perforator flaps. The total limb salvage rate was 98.8 percent. Total and partial flap failure rates were 6.1 percent and 9.0 percent, respectively. Comparing perforator recipients [n = 109 (25.8 percent)] to major artery recipients [n = 314 (74.2 percent)], there was no significant difference in total (p = 0.746) or partial flap failure (p = 0.212). Significant factors between the groups included larger flap size with major artery recipients (p = 0.001) and shorter operative time when using a perforator recipient (p = 0.012)., Conclusions: Perforator-to-perforator anastomosis is a reliable option that affords equivalent rates of flap success compared to major artery anastomosis in lower extremity reconstruction. The authors advocate using a major artery recipient in defects where the axial vessels are easily accessible. A perforator recipient is a viable alternative in defects where access to the axial vessels is inconvenient and in patients with limited recipient options., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background/aims: The diagnosis of intestinal tuberculosis (ITB) is often challenging. Therapeutic anti-tubercular trial (TATT) is sometimes used for the diagnosis of ITB. We aimed to evaluate the changing pattern of fecal calprotectin (FC) levels during TATT in patients with ITB., Methods: A retrospective review was performed on the data of 39 patients who underwent TATT between September 2015 and November 2018 in five university hospitals in Daegu, South Korea. The analysis was performed for 33 patients with serial FC measurement reports., Results: The mean age of the participants was 48.8 years. The final diagnosis of ITB was confirmed in 30 patients based on complete mucosal healing on follow-up colonoscopy performed after 2 months of TATT. Before starting TATT, the mean FC level of the ITB patients was 170.2 μg/g (range, 11.5-646.5). It dropped to 25.4 μg/g (range, 11.5-75.3) and then 23.3 μg/g (range, 11.5-172.2) after one and two months of TATT, respectively. The difference in mean FC before and one month after TATT was statistically significant (p<0.001), and FC levels decreased to below 100 μg/g in all patients after one month of TATT., Conclusion: All ITB patients showed FC decline after only 1 month of TATT, and this finding correlated with complete mucosal healing in the follow-up colonoscopy after 2 months of TATT.

Background: One of the critical factors for free flap survival is to maintain adequate perfusion. The authors evaluated the effect of epidural anesthesia on arterial maximal flow velocity of the free flap in microvascular lower extremity reconstruction., Methods: This is a prospective randomized study where patients were allocated to receive either combined general-epidural anesthesia (epidural group, n = 26) or general anesthesia alone (control group, n = 26). After injecting epidural ropivacaine 10 ml in the epidural group, the effect on arterial maximal flow velocity of the free flap was analyzed using ultrasonography. The primary outcome measurement was the arterial maximal flow velocity 30 minutes after establishing the baseline. Intraoperative hemodynamics and postoperative outcomes such as postoperative pain, opioid requirements, surgical complications, intensive care unit admission, and hospital length of stay were also assessed., Results: The arterial maximal flow velocity 30 minutes after the baseline measurement was significantly higher in the epidural group (35.3 ± 13.9 cm/second versus 23.5 ± 8.4 cm/second; p = 0.001). The pain score at 1 hour postoperatively and opioid requirements at 1 and 6 hours postoperatively were significantly lower in the epidural group [3.0 (interquartile range, 2.0 to 5.0) versus 5.0 (interquartile range, 3.0 to 6.0), p = 0.019; 0.0 μg (interquartile range, 0.0 to 50.0 μg) versus 50.0 μg (interquartile range, 0.0 to 100.0 μg), p = 0.005; and 46.9 μg (interquartile range, 0.0 to 66.5 μg) versus 96.9 μg (interquartile range, 41.7 to 100.0 μg), p = 0.014, respectively]. There were no significant differences in intraoperative hemodynamics or other postoperative outcomes between the two groups., Conclusion: Epidural anesthesia increased the arterial maximal flow velocity of the free flap and decreased postoperative pain and opioid requirements in microvascular lower extremity reconstruction., Clinical Question/level of Evidence: Therapeutic, I., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Background/aims: Patient-reported outcomes (PROs) are essential for clinical decision making, conduction of clinical research, and drug application acquisition in functional gastrointestinal disorders. The aim of this study is to develop a PRO instrument and to determine the respondents' perception of the efficacy of therapeutic agents for functional dyspepsia (FD)., Methods: A self-evaluation questionnaire for dyspepsia (SEQ-DYSPEPSIA) was developed and validated through a structured process. The 2-week reproducibility was evaluated, and the construct validity was assessed by correlating the scores of SEQ-DYSPEPSIA (including typical and major FD symptom subscales). Finally, the response to medication was assessed by comparing the changes after 4 weeks of treatment., Results: A total of 193 Korean patients (age 48.5 ± 13.6 years, 69.4% women) completed the questionnaire. SEQ-DYSPEPSIA with 11 items had a good internal consistency (alpha = 0.770-0.905) and an acceptable test-retest reliability (intraclass correlation coefficient = 0.733-0.859). The self-evaluation questionnaire (SEQ)-major FD score highly correlated with the postprandial fullness/early satiety domain of the Patient Assessment of Gastrointestinal Symptom Severity Index (correlation coefficient r = 0.741, P < 0.001), Nepean Dyspepsia Index-Korean version (NDI-K) ( r = 0.839, P < 0.001), and NDI-K quality of life ( r = -0.275 to -0.344, P < 0.001). After medical treatment, decrease in the SEQ-typical FD and SEQ-major FD was significantly greater in the responder group than in nonresponder group ( P = 0.019 and P = 0.009, respectively)., Conclusion: This study suggests that the Korean version of SEQ-DYSPEPSIA has good reliability and validity, and can be a useful PRO measurement tool in patients with FD.

Background:  Transmetatarsal amputation (TMA) preserves functional gait while avoiding the need for prosthesis. However, when primary closure is not possible after amputation, higher level amputation is recommended. We hypothesize that reconstruction of the amputation stump using free tissue transfer when closure is not possible can achieve similar benefits as primarily closed TMAs., Methods:  Twenty-eight TMAs with free flap reconstruction were retrospectively reviewed in 27 diabetic patients with a median age of 61.5 years from 2004 to 2018. The primary outcome was limb salvage rate, with additional evaluation of flap survival, ambulatory status, time until ambulation, and further amputation rate. In addition, subgroup analysis was performed based on the microanastomosis type., Results:  Flap survival was 93% (26 of 28 flaps) and limb salvage rate of 93% (25 of 27 limbs) was achieved. One patient underwent a second free flap reconstruction. In the two failed cases, higher level amputation was required. Thirteen flaps had partial loss or other complications which were salvaged with secondary intension or skin grafts. Median time until ambulation was 14 days following reconstruction (range: 9-20 days). Patients were followed-up for a median of 344 days (range: 142-594 days). Also, 88% of patients reported good ambulatory function, with a median ambulation score of 4 out of 5 at follow-up. There was no significant difference between the subgroups based on the microanastomosis type., Conclusion:  TMA with free flap reconstruction is an effective method for diabetic limb salvage, yielding good functional outcomes and healing results., Competing Interests: None declared., (Thieme. All rights reserved.)

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the "proven GERD" with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett's mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Background: A superficial circumflex iliac artery perforator flap has several advantages, such as reduced thickness, minimal donor-site morbidity, and inconspicuous scar. However, the application of a superficial circumflex iliac artery perforator flap is restricted because of its limited pedicle length. The aim of this article was to outline the technical modifications of superficial circumflex iliac artery perforator flap elevation to obtain long pedicles., Methods: This is a prospective study of 31 consecutive patients who required a long pedicled superficial circumflex iliac artery perforator flap between September of 2016 and December of 2019 at the authors' center. According to a preoperatively marked pathway of the superficial branch of the superficial circumflex iliac artery, the superficial circumflex iliac artery perforator flap was designed. During the elevation, the design was modified according to the perforator location in the free-style technique. The characteristics of the patients and the flaps, including pedicle length, were recorded. The revision rate, complication rate, and need for a secondary procedure were analyzed., Results: The mean follow-up period was 563 days (range, 92 to 1383 days). The mean length of the pedicle obtained was 6.9 cm (range, 6 to 8 cm) from the point where the pedicle merges into the flap. Long pedicles were anastomosed to the main source vessel or branch without tension. No major complications were reported., Conclusions: Overcoming the short pedicle length of a superficial circumflex iliac artery perforator flap by designing the flap laterally and performing an intraflap dissection is a reliable option when a longer pedicle is required, irrespective of the specific anatomy of the superficial circumflex iliac artery., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2021 by the American Society of Plastic Surgeons.)

The microsurgical options for lower limb lymphedema is a challenge. In search to improve the overall result, we hypothesized it would be beneficial to add the functioning lymph nodes to vein anastomosis (LNVA) in addition to lymphovenous anastomosis (LVA). This is a retrospective study of 160 unilateral stage II & III lower extremity lymphedema comparing the outcome between the LNVA + LVA group and the LVA only group from May 2013 to June 2018. MRI was used to identify the functioning lymph nodes. Patient outcome, including lower extremity circumference, body weight, bio impedance test, and other data were analyzed to evaluate whether lymph nodes to vein anastomosis (LNVA) improved outcome. The LNVA + LVA group showed significantly better results for circumference reduction rate, body weight reduction rate, and extracellular fluid reduction rate of the affected limb as compared to the LVA only group for both stage II and III lymphedema. The MRI imaging revealed that 9 cases had no identifiable lymph nodes of the affected limb and 54 cases with a nonfunctioning lymph node upon exploration despite positive imaging. Correlation showed the lymph node size needed to be at least 8 mm in the MRI to be functional. The LNVA + LVA approach for lymphedema has the benefit of better reduction as compared to LVA alone in the lower limb as well as the suprapubic region. Preoperative MRI will help to identify the functioning lymph node by increasing the overall probability of positive outcome., Competing Interests: Declaration of Competing Interest All the authors of this manuscript do not have any conflict of interest to declare in relation to the content of this article., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Tegoprazan is a novel, fast- and long-acting potassium-competitive acid blocker that suppresses gastric acid secretion, which could benefit patients with non-erosive reflux disease (NERD), a type of gastroesophageal reflux disease., Aim: To evaluate the efficacy and safety profiles of tegoprazan compared with those of a placebo in Korean patients with NERD., Methods: In this phase 3, double-blind, placebo-controlled, multicentre study, 324 Korean patients with NERD were randomised into three treatment groups: tegoprazan 50 mg, tegoprazan 100 mg and placebo. These drugs were provided once daily for 4 weeks. The primary endpoint was the proportion of patients with complete resolution of major symptoms (both heartburn and regurgitation) for the last 7 days of the 4-week treatment period. Other outcomes related to efficacy, safety and tolerability were also evaluated., Results: Among all, 42.5% (45/106), 48.5% (48/99) and 24.2% (24/99) of patients showed complete resolution of major symptoms at week 4 after receiving tegoprazan 50 mg, tegoprazan 100 mg, and placebo, respectively. Both doses of tegoprazan showed superior efficacy than the placebo (P = 0.0058 and P = 0.0004, respectively). The complete resolution rates of heartburn and proportions of heartburn-free days (as other efficacy outcomes) were significantly higher in both tegoprazan groups than in the placebo group (P < 0.05 for all). No significant difference in the incidence of treatment-emergent adverse events were noted., Conclusions: Tegoprazan 50 and 100 mg showed superior therapeutic efficacy compared with the placebo, as well as a favourable safety profile in patients with NERD. Registration number: ClinicalTrials.gov identifier NCT02556021., (© 2021 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Although the effects of botulinum toxin A on hernia reconstruction have been consistently reported, few studies provide objective evidence. The authors aimed to compare the effects of chemical component separation with those of mechanical component separation, and with a combination of chemical and mechanical component separation, in a rat hernia model., Methods: Rats were divided into four groups: 1, control; 2, chemical component separation; 3, mechanical component separation; and 4, chemical and mechanical component separation. Four weeks after hernia induction, botulinum toxin A was injected into groups 2 and 4. Hernia repair was performed 2 weeks after chemical component separation when mechanical component separation was performed in groups 3 and 4. Pretreatment and posttreatment defect sizes, traction forces, intraabdominal pressure, and hernia recurrences were analyzed., Results: The defect size was significantly decreased in groups 2 and 4 after chemical component separation. The traction force was significantly smaller in groups 2 and 3 compared with the control group, and the effects of chemical and mechanical component separation were additive. The mean intraabdominal pressure was 16.83 mmHg in group 1, 10.67 mmHg in group 2, 10.17 mmHg in group 3, and 9.67 mmHg in group 4, thus showing significant reductions following chemical and mechanical component separation. Recurrence was observed in all six animals (100 percent) in groups 1 and 3, but in only one of six (17 percent) in groups 2 and 4., Conclusions: Preoperative botulinum toxin A significantly reduces hernia size (by 30 percent) and the traction force required to medialize the rectus abdominis. After hernia repair, chemical component separation decreases the intraabdominal pressure to a similar degree as mechanical component separation, but only chemical component separation appears to reduce hernia recurrence., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Clostridium perfringens is a well-known pathogen that causes food-borne illnesses. Although bacteriophages can be effective natural food preservatives, phage endolysin and cell wall-binding domain (CBD) provide useful materials for lysis of C. perfringens and rapid detection. The genome of phage CPAS-15 consists of 51.8-kb double-stranded circular DNA with 78 open reading frames, including an endolysin gene. The apparent absence of a virulence factor or toxin gene suggests its safety in food applications. C. perfringens endolysin (LysCPAS15) inhibits host cells by up to a 3-log reduction in 2 h, and enhanced green fluorescent protein (EGFP)-fused CBD protein (EGFP-LysCPAS15&#95;CBD1) detects C. perfringens within 5 min. Both exhibit broader host range spectra and higher stabilities than a bacteriophage. Tests in milk show the same host lysis and specific detection activities, with no hindrance effect from food matrices, indicating that endolysin and its CBD can provide food extended protection from C. perfringens contamination., (Copyright © 2020. Published by Elsevier Ltd.)

In order to provide a physiological solution for patients with breast cancer-related lymphedema (BCRL), the surgeon must understand where and how the pathology of lymphedema occurred. Based on each patient's pathology, the treatment plan should be carefully decided and individualized. At the authors' institution, the treatment plan is made individually based on each patient's symptoms and relative factors. Most early-stage patients first undergo decongestive therapy and then, depending on the efficacy of the treatment, a surgical approach is suggested. If the patient is indicated for surgery, all the points of lymphatic flow obstruction are carefully examined. Thus a BCRL patient can be considered for lymphaticovenous anastomosis (LVA), a lymph node flap, scar resection, or a combination thereof. LVA targets ectatic superficial collecting lymphatics, which are located within the deep fat layer, and preoperative mapping using ultrasonography is critical. If there is contracture on the axilla, axillary scar removal is indicated to relieve the vein pressure and allow better drainage. Furthermore, removing the scars and reconstructing the fat layer will allow a better chance for the lymphatics to regenerate. After complete removal of scar tissue, a regional fat flap or a superficial circumflex iliac artery perforator flap with lymph node transfer is performed. By deciding the surgical planning for BCRL based on each patient's pathophysiology, optimal outcomes can be achieved. Depending on each patient's pathophysiology, LVA, scar removal, vascularized lymph node transfer with a sufficient adipocutaneous flap, and simultaneous breast reconstruction should be planned.

Vibrio vulnificus is a well-known opportunistic pathogen causing food-borne illnesses by ingestion of contaminated seafood. A new strain of V. vulnificus FORC&#95;016 was isolated from a patient's blood sample in South Korea. The genome consists of two circular DNA chromosomes: chromosome I (3,234,424 bp with a G + C contents of 46.60% containing 2,889 ORFs, 106 tRNA genes, and 31 rRNA genes) and chromosome II (1,837,945 bp with a GC content of 47.00% containing 1,572 ORFs, 13 tRNA genes, and 3 rRNA genes). In addition, chromosome I has a super integron (SI) containing 209 ORFs, which is probably associated with various additional functions including antibiotic resistance and pathogenicity. Pan-genome analysis with other V. vulnificus genomes revealed that core genome regions contain most of the important virulence factors. However, accessory genome regions are located in the SI region and contain unique genes regarding cell wall biosynthesis and generation of host cell protecting capsule, suggesting possible resistance ability against environmental stresses. Comparative RNA-Seq analysis of samples between contact and no contact to the crab conditions showed that expressions of amino acid/peptide and carbohydrate transport and utilization genes were down-regulated, but expressions of cell division and growth-related genes were up-regulated, suggesting that the crab may be a nutrition reservoir for rapid propagation of V. vulnificus . Therefore, consumption of the contaminated fresh crab would provide a large number of V. vulnificus to humans, which may be more dangerous. Consequently, biocontrol of V. vulnificus may be critical to ensure the safety in seafood consumption., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kim, Chung, Kwon, Choi and Lee.)

Background and Aim: The few studies concerning the association between sleep disorders and functional dyspepsia (FD) have yielded inconsistent results. We compared the prevalence of sleep disorders in patients with FD and healthy controls, and evaluated whether FD was independently associated with sleep disorders, and the risk factors for sleep disorders in patients with FD., Methods: This prospective, multicenter, cross-sectional study was conducted from August 2014 to December 2017 at 12 hospitals in South Korea. The inclusion criterion was the presence of FD (for ≥18 years) according to the Rome III criteria. Healthy controls were recruited from among patients who visited the Health Examination Center for check-ups., Results: In total, 526 subjects were prospectively enrolled in this study (201 with FD and 325 healthy controls). The prevalence of sleep disorders was significantly higher among the patients with FD than among the healthy controls (41.8% vs 18.8%, P = 0.000). In a multivariate analysis, FD (odds ratio [OR] = 1.851; 95% confidence interval [CI] 1.194-2.870; P = 0.006), female sex (OR = 1.672; 95% CI 1.063-2.628; P = 0.026), and anxiety (OR = 3.325; 95% CI 2.140-5.166; P = 0.000) were independent risk factors for sleep disorders in the overall cohorts. In patients with FD only, low body mass index, heartburn, and anxiety were independent risk factors for sleep disorders in a further multivariate analysis., Conclusion: Sleep disorders were common in patients with FD. FD was significantly associated with sleep disorders in our patient population, irrespective of the presence of heartburn or psychiatric disorders., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

To study pathogenesis and toxicity of Staphylococcus aureus in foods, FORC&#95;062 was isolated from a human blood sample and complete genome sequence has a type II SCCmec gene cluster and a type II toxin-antitoxin system, indicating an MRSA strain. Its mobile gene elements has many pathogenic genes involved in host infection, biofilm formation, and various enterotoxin and hemolysin genes. Clinical MRSA is often found in animal foods and ingestion of MRSA-contaminated foods causes human infection. Therefore, it is very important to understand the role of contaminated foods. To elucidate the interaction between clinical MRSA FORC&#95;062 and raw chicken breast, transcriptome analysis was conducted, showing that gene expressions of amino acid biosynthesis and metabolism were specifically down-regulated, suggesting that the strain may import and utilize amino acids from the chicken breast, but not able to synthesize them. However, toxin gene expressions were up-regulated, suggesting that human infection of S. aureus via contaminated food may be more fatal. In addition, the contaminated foods enhance multiple-antibiotic resistance activities and virulence factors in this clinical MRSA. Consequently, MRSA-contaminated food may play a role as a nutritional reservoir as well as in enhancing factor for pathogenesis and toxicity of clinical MRSA for severe food-borne outbreaks., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background/aims: Prokinetics such as mosapride citrate CR (conventional-release; Gasmotin) are commonly used in functional dyspepsia (FD). This study aims to evaluate the efficacy and safety of once-a-day mosapride citrate SR (DWJ1252), a sustained-release formulation of mosapride citrate, compared with mosapride citrate CR 3 times a day, in patients with FD., Methods: In this multicenter, randomized, double-blind, active-controlled, non-inferiority study, 119 patients with FD (by the Rome III criteria, 60 for mosapride citrate SR and 59 for mosapride citrate CR) were randomly allocated to mosapride citrate SR once daily or mosapride citrate CR thrice daily for 4 weeks in 16 medical institutions. Primary end point was the change in gastrointestinal symptom (GIS) score from baseline, assessed by GIS questionnaires on 5-point Likert scale after 4-week treatment. Secondary end points and safety profiles were also analyzed., Results: The study included 51 and 49 subjects in the mosapride citrate SR and mosapride citrate CR groups, respectively. GIS scores at week 4 were significantly reduced in both groups (mean ± SD: -10.04 ± 4.45 and -10.86 ± 5.53 in the mosapride citrate SR and mosapride citrate CR groups, respectively; P < 0.001), and the GIS changes from baseline did not differ between the 2 groups (difference, 0.82 point; 95% CI, -1.17, 2.81; P = 0.643). Changes in GIS at weeks 2 and 4 and quality of life at week 4, and the improvement rates of global assessments at weeks 2 and 4, did not differ between the groups. Adverse events were similar in the 2 groups, and there were no serious adverse events., Conclusion: In patients with FD, mosapride citrate SR once daily is as effective as mosapride citrate CR thrice daily, with a similar safety profile.

Background: When a patient with breast cancer-related lymphedema (BCRL) depends on continuous compression management, that is, when interstitial fluid accumulation is continuously ongoing, surgical treatment should be considered. Physiologic surgery is considered more effective for early-stage lymphedema. The purpose of this study was to identify predictors of patients with BCRL who will be compression-dependent despite 2 years of conservative care., Methods: This study included patients with BCRL who followed up for 2 years. Patients were classified into two groups (compression-dependent vs. compression-free). We identified the proportion of compression-dependent patients and predictors of compression dependence., Results: Among 208 patients, 125 (60.1%) were classified into the compression-dependent group. Compression dependence was higher in patients with direct radiotherapy to the lymph nodes (LNs), those with five or more LNs resections, and those with BCRL occurring at least 1 year after surgery., Conclusions: BCRL patients with direct radiotherapy to the LNs, extensive LN dissection, and delayed onset may be compression-dependent despite 2 years of conservative care. Initially moderate to severe BCRL and a history of cellulitis also seem to be strongly associated with compression dependence. Our results allow for the early prediction of compression-dependent patients who should be considered for physiologic surgery.

Adolescent Internet addiction is an important social issue entailing extensive use of Internet and smartphones and its side effects. This study identified relevant psychological factors that affect excessive Internet use (EIU) and excessive smartphone use (ESU) in adolescents using structural equation modeling (SEM). A sample of 714 individuals drawn from lists of middle school students in South Korea completed self-administered questionnaires, including Young's Internet Addiction Test (Y-IAT), the Smartphone Addiction Scale (SAS), and various clinical and psychological scales measuring depression, anxiety, attention deficit/hyperactivity disorder (ADHD), aggression, expression of anger, and the behavioral inhibition system (BIS)/activation system (BAS). The final model, fitted using SEM, showed that both clinical characteristics, including ADHD symptoms, aggression, expression of anger, depression, and anxiety, and personality characteristics, represented by BIS/BAS, played important roles in the severity of EIU or ESU. In particular, affective components such as depression and anxiety were significantly associated with both EIU and ESU, whereas aggression, the expression of anger, and ADHD symptoms affected only EIU. Furthermore, the association between ESU and EIU was significant. Although personality characteristics measured by the BIS and BAS scores did not have direct effects on addiction, they were associated with clinical features and might be risk factors for addiction. The model revealed significant pathways from personality and clinical features to EIU and ESU in adolescents and informed our basic understanding of the meaningful predictors of these addictions and their direct and indirect influences., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Although many attempts have been made to augment the volume of the latissimus dorsi (LD) myocutaneous flap in breast reconstruction, only a few studies on the shaping of the LD flap to achieve a natural native breast have been conducted. We introduce our novel method to reconstruct a naturally shaped breast by combining an extended LD myocutaneous flap with immediate lipofilling., Methods: The patients who underwent an immediate unilateral breast reconstruction with an extended LD myocutaneous flap and lipofilling were retrospectively reviewed. The extended LD myocutaneous flap in 180-degree rotation was combined with an immediate lipofilling procedure followed by suturing to reproduce the constant dimensions of a neobreast., Results: A total of 45 patients with a mean age of 46 years and an average body mass index of 23.1 kg/m were enrolled. The average weight of the mastectomy specimens was 299.0 g. An average 18.8 × 8.7-cm skin paddle within the flap was harvested, and 71.0 mL of fat was injected into the flap. Donor site seroma was found in 9 patients, and no flap or fat necrosis was found., Conclusions: Our technique of extended LD muscle flap with lipofilling reproduced breasts with constant dimensions and appropriate width, height, and projection. Shaping the LD muscle flap is not difficult or unpredictable. This is a simple and easy technique to shape the LD flap and will provide surgeons with an additional autologous option for breast reconstruction.

Background:  With the technological advances, microsurgery has evolved to the era of supermicrosurgery since its inception. With the popularization of these flaps, proficiency in using tools such as color Doppler ultrasound (CDU) has become crucial. Despite the increased interest, studies regarding the role of ultrasound in microsurgical reconstruction are scarce. Therefore, in this study, we discussed currently available imaging modalities for reconstructive surgeons, types of ultrasound, and the role of ultrasound in microsurgical reconstruction, and made recommendations for ultrasound use in reconstructive surgery., Methods:  We performed a computerized search of ultrasound in reconstructive surgery using the MEDLINE database. Data regarding ultrasound indications, usage, and outcomes were collected., Results:  Of the 115 articles identified, the majority was written on nonreconstructive ultrasound uses (51.4%). For the reconstructive uses, mapping of perforators was the most common usage (39.1%), followed by flap monitoring and volume measurement. In addition, we found that there are a limited number of literature on the role of CDU in reconstructive surgery, especially on its intraoperative and postoperative use., Conclusion:  CDU is a valuable and powerful tool for any reconstructive surgeons who are interested in performing microsurgery or supermicrosurgery. As the demand of customized flaps using superthin flaps, perforator-to-perforator anastomosis, and supermicrosurgery increases, understanding and becoming versatile in CDU will be critical. We hope our experience with using ultrasound and refinements that we made are helpful for those who would like to include it as a part of their armamentarium., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)