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Objectives: Endoscopic resection (ER) for gastric submucosal tumors (SMTs) has gained prominence in recent years, with studies emerging from various countries. However, there is a paucity of reports from Japan. We aimed to elucidate the efficacy and safety of ER for gastric SMT in Japan. Methods: In this retrospective observational study, we investigated the outcomes of consecutive patients who underwent ER for gastric SMT from January 2017 to May 2023. The outcome variables assessed included the complete resection rate, procedure time, closure-related outcomes, and the incidence of adverse events. Results: A total of 13 patients were included in the analysis. The median procedure time was 163 (55-283) min. Complete full-thickness resection was performed in seven cases, while in four cases, the serosa remained, and in two cases, the outer layer of the muscularis propria remained. In two cases where the SMT was located on the anterior side, conversion to laparoscopic surgery became necessary, resulting in a procedural success rate of 84.6% (11/13). Excluding these two cases, endoscopic closure of the defect was successfully accomplished in the remaining 11 cases. R0 resection was achieved in 12 out of 13 cases (92.3%). Although one patient had peritonitis, which was successfully treated conservatively, no other treatment-related adverse events were encountered. Conclusions: Although ER for SMT on the anterior side may be challenging, our experience revealed that ER is a safe and efficacious approach for gastric SMT.
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OBJECTIVES: The gastroesophageal junction (GEJ) consists of various anatomical components that together form a barrier to prevent reflux of gastric content. This study introduces a novel phase concept to dynamically evaluate the antireflux barrier (ARB) during endoscopy and analyzes its functionality. METHODS: We reviewed previously the recorded endoscopic videos of subjects who underwent the endoscopic pressure study integrated system (EPSIS) from February to April 2024 for indications other than gastroesophageal reflux disease symptoms. This device was used as an auxiliary tool to measure intragastric pressure (IGP) during endoscopy with a retroflex view. The ARB dynamic was divided into three phases: Phase I (gastric phase), Phase II (lower esophageal sphincter phase), and Phase III (esophageal clearance phase). We evaluated the morphological changes in the ARB during insufflation using EPSIS. RESULTS: The median age of the 30 subjects was 58 years (interquartile range [IQR] 46.5-68.8), including 20 men and 10 women. Endoscopic findings and IGPs were recorded during the three phases. In Phase I, at low IGP (median 6.75 mmHg), the gastroesophageal flap valve and longitudinal folds were observed in 80% of cases. In Phase II, at moderate IGP (median 11.8 mmHg), the scope holding sign was observed in 86.7%. In Phase III, at high IGP (median 19 mmHg) inducing belching, peristalsis was observed in 80% of cases with median recovery time of 5 s. CONCLUSION: The phase concept provides a valuable framework for understanding the antireflux mechanism. Further research is needed to validate these findings in GEJ disorders and explore correlations with other modalities.
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OBJECTIVES: The endoscopic pressure study integrated system (EPSIS) is an endoscopic diagnostic system utilized for evaluation of lower esophageal sphincter function. Although previous studies have determined that EPSIS was effective as a tool for the diagnosis of achalasia, it remains uncertain if EPSIS can detect significant changes before and after peroral endoscopic myotomy (POEM), which is the premier treatment for achalasia. This study aimed to evaluate the effectiveness of EPSIS as an objective diagnostic tool for assessing the clinical effect of POEM. METHODS: We conducted a retrospective analysis of patients who underwent POEM from January 2022 to December 2023. The patients underwent EPSIS preoperatively and 2 months postoperatively. Intragastric pressure (IGP) parameters, including the maximum IGP, IGP difference, and waveform gradient were compared pre- and post-POEM. These parameters also were compared between two groups: the postoperative gastroesophageal reflux disease (GERD) group and the non-GERD group. RESULTS: A total of 50 patients were analyzed. The mean maximum IGP was significantly lower postoperatively than preoperatively (15.0 mmHg vs. 19.8 mmHg, P < 0.001). The mean IGP difference and waveform gradient were also significantly lower postoperatively than preoperatively (8.0 mmHg vs. 12.2 mmHg, P < 0.001; and 0.26 mmHg/s vs. 0.43 mmHg/s, P < 0.001, respectively). The mean postoperative waveform gradient was significantly lower in the GERD group (17 patients, 34%) than in the non-GERD group (33 patients, 66%) (0.207 mmHg vs. 0.291 mmHg, P = 0.034). CONCLUSION: The results supported the use of EPSIS as an effective diagnostic tool for assessing the effect of POEM.
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Video 1XXX.
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Video 1Introducing the dead space eliminating technique (DET), a closure method using anchor pronged clips for antireflux mucoplasty in treating proton pump inhibitor refractory-dependent GERD. DET ensures comprehensive dead space elimination during closure.
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The field of minimally invasive endoscopic treatment has seen a continual progression, marked by significant advancements in treatment devices and the refinement of endoscopic techniques. While endoscopic resection has become the standard for treating superficial gastrointestinal neoplasms, a proactive approach becomes imperative when dealing with lesions that extend beyond the submucosal layer and deeper into the muscularis propria. The ongoing evolution of endoscopic closure techniques has facilitated the introduction of advanced procedures such as endoscopic muscularis dissection, endoscopic subserosal dissection, and endoscopic full-thickness resection. This evolution is achieved by the commitment to improve the efficacy and precision in treating challenging lesions. Nevertheless, there is currently a lack of definitive guidelines or consensus regarding the specifics of deeper layer dissection. Drawing from prior research and clinical insights, this review discusses indications, techniques, clinical outcomes, and future perspectives of deeper layer dissection.
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Procedimentos Cirúrgicos Minimamente Invasivos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Ressecção Endoscópica de Mucosa/métodos , Endoscopia Gastrointestinal/métodos , Neoplasias Gastrointestinais/cirurgia , Neoplasias Gastrointestinais/patologiaAssuntos
Barreira de Filtração Glomerular , Glomérulos Renais , Receptores Acoplados a Proteínas G , Animais , Glomérulos Renais/metabolismo , Humanos , Barreira de Filtração Glomerular/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/fisiologia , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , CamundongosRESUMO
Iridoids, which are a class of monoterpenoids, are attractive synthetic targets due to their diversely substituted cis-fused cyclopenta[c]pyran skeletons. Additionally, various biological activities of iridoids raise the value of synthetic studies on this class of compounds. Here, our synthetic efforts toward 11-noriridoids; (±)-umbellatolide B (6), (±)-10-O-benzoylglobularigenin (9) and 1-O-pentenylaucubigenin (34) are described. For the efficient synthesis of target compounds, common synthetic intermediates (tricyclic enones 17 and 26) were prepared by the Pauson-Khand reaction. The cleavage of the acetal bond on the tricyclic enones and 1,2-reduction introduced the two hydroxy groups on the cyclopentane ring of the core scaffold. Furthermore, the C3-C4 olefin part was constructed by the syn-elimination of a thiocarbonate moiety to obtain 34. The developed synthetic routes for 6, 9, and 34 will be useful for the preparation of iridoid analogs that have a polyfunctionalized core skeleton.
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Iridoides , Iridoides/síntese química , Iridoides/química , Estrutura Molecular , EstereoisomerismoRESUMO
Video 1XXX.
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MraY (phospho-N-acetylmuramoyl-pentapeptide-transferase) inhibitory natural products are attractive molecules as candidates for a new class of antibacterial agents to combat antimicrobial-resistant bacteria. Structural optimization of these natural products is required to improve their drug-like properties for therapeutic use. However, chemical modifications of these natural products are painstaking tasks due to complex synthetic processes, which is a bottleneck in advancing natural products to the clinic. Here, we develop a strategy for a comprehensive in situ evaluation of the build-up library, which enables us to streamline the preparation of the analogue library and directly assess its biological activities. We apply this approach to a series of MraY inhibitory natural products. Through construction and evaluation of the 686-compound library, we identify promising analogues that exhibit potent and broad-spectrum antibacterial activity against highly drug-resistant strains in vitro as well as in vivo in an acute thigh infection model. Structures of the MraY-analogue complexes reveal distinct interaction patterns, suggesting that these analogues represent MraY inhibitors with unique binding modes. We further demonstrate the generality of our strategy by applying it to tubulin-binding natural products to modulate their tubulin polymerization activities.
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Antibacterianos , Proteínas de Bactérias , Produtos Biológicos , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Animais , Camundongos , Humanos , Transferases (Outros Grupos de Fosfato Substituídos)RESUMO
We investigated the reactivity of P2-type honeycomb layered oxides Na2Ni2TeO6 (NNTO) and Na2Zn2TeO6 (NZTO) co-fired at the temperature from 500 °C to 800 °C. From X-ray diffraction measurements, it was found that the reaction between NNTO and NZTO is unremarkable at the temperature below 700 °C. However, when annealed at 800 °C, they formed the solid-solution phase without any secondary phases. The NNTO and NZTO composite pellets co-fired at 800 °C showed sodium-ion conductivity well above 10-4 S cm-1 at room temperature, indicating that the solid-solution phase of NNTO and NZTO has good ionic conductivity. A maximum room temperature conductivity of 7.4 × 10-4 S cm-1 was confirmed at the mixing ratio NNTO: NZTO = 0.5 : 1.5. These results can be applied to the fabrication of all-solid-state batteries using NNTO as the cathode active material and NZTO as the solid electrolyte via a simple co-sintering process.
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OBJECTIVES: The endoscopic pressure study integrated system (EPSIS) represents an innovative approach for evaluating lower esophageal sphincter function by monitoring intragastric pressure using diagnostic gastroscopes. This study aimed to assess the feasibility and validity of employing ultrathin gastroscopes for EPSIS. METHODS: A retrospective analysis was conducted on a database of consecutive patients who underwent EPSIS using both ultrathin and regular gastroscopes between September 2021 and October 2023. The study compared EPSIS parameters between the two gastroscope types to evaluate the correlation of key metrics. RESULTS: Thirty patients underwent EPSIS with both ultrathin and regular gastroscopes. Significant positive correlations were observed in the pressure waveform: maximum intragastric pressure (mmHg) (ρ = 0.82, P < 0.001) and intragastric pressure gradient (mmHg/s) (ρ = 0.80, P < 0.001) when comparing the two gastroscopes. Maximum intragastric pressure (15.5 [5.3-20.3] vs. 18.5 [3.4-21.6], P < 0.001) and pressure gradient (0.16 [0.013-0.41] vs. 0.24 [0.0039-1.13], P < 0.001), (median [range]) were significantly lower with ultrathin gastroscopes. CONCLUSIONS: This study establishes that EPSIS parameters obtained with an ultrathin gastroscope exhibit a significant correlation with those obtained using a regular gastroscope, with each EPSIS parameter consistently lower. These findings support the viability of EPSIS for ultrathin gastroscopy and highlight its potential as a diagnostic tool for assessing lower esophageal sphincter function.
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Predictive processing in the brain, involving interaction between interoceptive (bodily signal) and exteroceptive (sensory) processing, is essential for understanding music as it encompasses musical temporality dynamics and affective responses. This study explores the relationship between neural correlates and subjective certainty of chord prediction, focusing on the alignment between predicted and actual chord progressions in both musically appropriate chord sequences and random chord sequences. Participants were asked to predict the final chord in sequences while their brain activity was measured using electroencephalography (EEG). We found that the stimulus preceding negativity (SPN), an EEG component associated with predictive processing of sensory stimuli, was larger for non-harmonic chord sequences than for harmonic chord progressions. Additionally, the heartbeat evoked potential (HEP), an EEG component related to interoceptive processing, was larger for random chord sequences and correlated with prediction certainty ratings. HEP also correlated with the N5 component, found while listening to the final chord. Our findings suggest that HEP more directly reflects the subjective prediction certainty than SPN. These findings offer new insights into the neural mechanisms underlying music perception and prediction, emphasizing the importance of considering auditory prediction certainty when examining the neural basis of music cognition.
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Potenciais Evocados Auditivos , Música , Humanos , Estimulação Acústica , Potenciais Evocados Auditivos/fisiologia , Percepção Auditiva/fisiologia , Incerteza , Eletroencefalografia , Música/psicologiaRESUMO
BACKGROUND AND AIM: Anti-reflux mucosal ablation (ARMA) is an emerging endoscopic treatment aimed at enhancing the gastroesophageal junction flap valve. This study aimed to evaluate its feasibility, effectiveness, and safety. METHODS: Between May 2018 and December 2022, patients with gastroesophageal reflux disease (GERD) symptoms refractory to acid suppression medications or those dependent on such medications were enrolled for ARMA. This retrospective analysis utilized prospectively collected data from an international bi-center study. GERD questionnaire, upper endoscopy, and 24-h pH monitoring were conducted at 2-6 months and 12 months post-ARMA. Clinical success was defined as a > 50% reduction in a validated GERD questionnaire. RESULTS: A total of 68 patients underwent ARMA. Definitive GERD was diagnosed in 44 (64.7%) patients, while 24 (35.3%) exhibited reflux hypersensitivity. Clinical success rates at 2-6 months and 1 year post-ARMA were 60% (39/65) and 70% (21/30), respectively. The median GERD-health-related quality of life score significantly improved from 26 to 11 at 2-6 months (P < 0.001). Among the 51 patients (71.8%) who underwent 24-h pH monitoring, the median acid exposure time decreased from 5.3% to 0.7% (P = 0.003), accompanied by a significant reduction in esophagitis rates (P < 0.001). Multivariate analysis did not identify predictors of short-term success. Nine (13.2%) patients experienced transient stenosis requiring balloon dilation. CONCLUSIONS: ARMA demonstrates both technical feasibility and reproducibility as a safe procedure that effectively ameliorates GERD symptoms in approximately two-thirds of patients during short-term follow up. Both reflux hypersensitivity and confirmed GERD patients, regardless of their response to acid suppression medication, may be suitable candidates.
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Refluxo Gastroesofágico , Qualidade de Vida , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Refluxo Gastroesofágico/complicações , Endoscopia GastrointestinalRESUMO
BACKGROUND & AIM: Peroral endoscopic myotomy (POEM) is a safe and effective endoscopic treatment for achalasia and other esophageal motility disorders, and TTJ (Triangle Tip Knife J; Olympus, Tokyo, Japan) is currently widely used in POEM. Recently, we reported a novel modification of TTJ, which was adjusted to knife length 2 mm by attaching a disposable clip (QuickClip Pro; Olympus) sheath to the tip as a hood attachment. In this study, we compared the safety and effectiveness of TTJ and TTJ with hood attachment (TTJ-H) in POEM. METHODS: In this 1:1 propensity score matched retrospective cohort study, we compared the procedure time, myotomy efficiency, number of coagulation forceps usage, adverse events, length of hospital stay after POEM, procedural success and clinical success between TTJ and TTJ-H groups. RESULTS: We examined 682 consecutive patients who underwent POEM between January 2021 and June 2023. We excluded 134 patients who had already undergone POEM or laparoscopic Heller myotomy as prior myotomy. Finally, we identified 98 propensity score-matched pairs (n = 196). The mean procedure time was shortened from 93.5 to 80.2 min (14% reduction, P = 0.012) when comparing TTJ-H group to TTJ group. The mean myotomy efficiency was improved from 2.76 to 2.32 min/cm (16% improvement, P = <0.001), and usage of coagulation forceps for hemostasis was decreased from 3.87 to 0.55 (86% reduction, P = <0.001). CONCLUSIONS: This study showed that use of TTJ-H could reduce total procedure time, improve myotomy efficiency, and reduce costs compared to TTJ.
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BACKGROUND AND AIMS: Killian-Jamieson diverticulum (KJD) is a relatively uncommon variant of pharyngoesophageal diverticula, distinct from the more prevalent Zenker diverticulum. However, literature on endoscopic management of KJD remains limited. This study aimed to elucidate the efficacy and safety of peroral endoscopic septotomy (POES) as a treatment approach for symptomatic KJD. METHODS: In this retrospective observational study, we investigated the outcomes of nine consecutive patients who underwent POES for KJD between January 2019 and May 2023. Follow-up data of at least 2 months post-treatment were analyzed. The primary outcome measure was the technical success rate of POES. Secondary outcomes encompassed the clinical success rate, defined as symptomatic improvement 2 months after POES, and the incidence of adverse events. RESULTS: All patients presented with dysphagia, with a median symptom duration of 6 months (interquartile range [IQR]: 3-12 months). The median diverticulum size was 32 mm (IQR: 24-42 mm). The median duration of the operation time was 66 min (IQR: 60-109). A 100% technical success rate was achieved, with complete closure of the defect in all cases. There were no adverse events related to this treatment. The median hospitalization duration was 5 days (IQR: 4-6), and the clinical success rate was 88.9%. Follow-up barium esophagograms exhibited significant improvement in the flow of the barium for all patients. CONCLUSIONS: Despite the relatively limited case volume, our findings underscore that POES is a safe and efficacious approach for managing symptomatic KJD.
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Video 1We present a new therapeutic approach called antireflux mucoplasty for proton pump inhibitor-refractory GERD.
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OBJECTIVES: Anti-reflux mucosectomy (ARMS) and anti-reflux mucosal ablation (ARMA) were developed as interventions for proton pump inhibitor (PPI)-refractory/-dependent gastroesophageal reflux disease (GERD). Although ARMS and ARMA are established treatments for PPI-refractory GERD, reliance on natural healing for ulcer scar formation introduces uncertainty and bleeding risk. To address these issues, we introduced a novel approach called anti-reflux mucoplasty (ARM-P), which involves immediate closure of mucosal defects following mucosectomy. This pilot study aims to evaluate the safety, feasibility, and efficacy of ARM-P. METHODS: A retrospective single-center study was conducted using prospectively collected data from October 2022 to July 2023. Patients with PPI-refractory/-dependent GERD who underwent ARM-P were included. The study evaluated technical success of ARM-P, before and after ARM-P GERD-Health Related Quality of Life Questionnaire, GerdQ, and Frequency Scale for the Symptoms of GERD scores, along with PPI discontinuation and endoscopic esophagogastric junction morphology. RESULTS: A total of 20 patients with a median age of 61.5 years underwent the ARM-P procedure. The procedure achieved 100% technical success without adverse events. After ARM-P, 55.0% discontinued PPI usage and 15.0% reduced PPI dose by half. Median GERD-Health Related Quality of Life Questionnaire score improved from 21 to 6 (P = 0.0026), median GerdQ score improved from 9 to 7 (P = 0.0022), and median Frequency Scale for the Symptoms of GERD score decreased from 16 to 7 (P = 0.0003). Median Hill's Classification significantly improved from grade III to grade I (P = 0.0001). CONCLUSIONS: This study presents the first pilot report of ARM-P, demonstrating its procedural safety, technical feasibility, and short-term efficacy.