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Competing Interests: The authors declare that they have no conflict of interest.

Background and Aims: This article systemically describes the landscape of peroral endoscopic myotomy (POEM)-related adverse events (AEs) and compares the different grading systems; and establishes and validates a combined risk factor model and a simplified risk-scoring system to predict POEM-related major AEs., Methods: A total of 3135 patients with achalasia treated with POEM were included and the AEs were systemically described and graded. A predictive model and risk-scoring system was developed using logistic regression and then internally validated using bootstrapping approaches., Results: A total of 258 out of 3135 patients, accounting for 8.23% of the total patients, presented with 297 AEs. According to Clavien-Dindo grading, 175 (67.83%), 23 (8.91%), 56 (21.71%), 4 (1.55%), and 0 (0.00%) patients were graded as grade I-V, respectively. By American Society of Gastrointestinal Endoscopy lexicon, 175 (67.83%) patients were classified with mild AE, 66 (25.58%) were classified with moderate AE, and 17 (6.59%) were classified with severe AE, respectively. Sixty-eight (2.17%) patients were classified with major AE. Air insufflation, selective myotomy, mucosal injury, and long operation time were selected into the predictive model with an area under the curve of 0.795. They were assigned with scores of 18, 5, 3, and 5 in the risk-scoring system, respectively. By applying the risk scoring system, patients with higher scores had higher rates of major AEs. The model showed little evidence for overfitting and was well-calibrated., Conclusions: Based on a systematic landscape analysis, POEM is a safe procedure with low rates of severe AEs. Our prediction model and risk-scoring system demonstrated good performance in predicting major AEs., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Idiopathic achalasia (IA) is a severe motility disorder characterized by neuronal degeneration in the myenteric plexus, but the etiology remains largely unknown. We performed whole-exome sequencing (WES) in 100 IA-affected individuals and 313 non-IA control subjects and validated the results in 230 IA-affected individuals and 1,760 non-IA control subjects. Common missense variants rs1705003 (CUTA, GenBank: NC_000006.11:g.33385953A>G) and rs1126511 (HLA-DPB1, GenBank: NC_000006.11:g.33048466G>T) at 6p21.32 were reproducibly associated with increased risk of IA (rs1126511: OR = 1.83, p = 2.34 × 10 -9 ; rs1705003: OR = 2.37, p = 3.21 × 10 -7 ), meeting exome-wide significance. Both variants can affect the expression of their target genes at the transcript level. An array-based association analysis in 280 affected individuals and 1,121 control subjects determined the same signal at 6p21.32. Further conditional analyses supported that the two missense variants identified in WES-based association study were potential causal variants of IA. For rare variants, the top genes identified by gene-based analysis were significantly enriched in nerve and muscle phenotypic genes in the mouse. Moreover, the functional rare variants in these genes tended to cooccur in IA-affected individuals. In an independent cohort, we successfully validated three rare variants (CREB5, GenBank: NC_000007.13:g.28848865G>T; ESYT3, GenBank: NC_000003.11:g.138183253C>T; and LPIN1, GenBank: NC_000002.11:g.11925128A>G) which heightens the risk of developing IA. Our study identified and validated two common variants and three rare variants associated with IA in immunologic and neurological genes, providing new insight into the etiology of IA., (Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background and Aim. After routine fasting for patients with achalasia before POEM (peroral endoscopic myotomy) procedure, solid contents may still remain in the esophagus. We aimed to compare the efficacy and patient satisfaction in patients with and without drinking large amounts of carbonated beverages preoperatively. Methods. This retrospective study enrolled 65 achalasia patients who underwent POEM from June 2017 to October 2021. Based on the preoperative diet strategies, patients were divided into carbonated beverage group (n = 48) and control group (n = 17). Demographic and clinical data, duration of preoperative endoscopy, quality of esophagus cleansing, and patient satisfaction on preoperative procedure were collected and compared. In the current study, we established the quality of esophagus cleansing: Grade A, no remnants or only liquid or frothy discharge; Grade B, a little amount of solid content remained; and Grade C, a large amount of solid content remained. Results. There were 41 Grade A, 6 Grade B, and 1 Grade C patients in the carbonated beverage group, while there were 8 Grade A, 6 Grade B, and 3 Grade C patients in the control group (p value = 0.001). The esophagus cleansing degrees were significantly ameliorated after drinking carbonated beverages in all the three subtypes of achalasia according to the degree of dilatation. The mean duration of preoperative endoscopy was 6.54 ± 2.250 minutes in the carbonated beverage group and 10.27 ± 4.788 minutes in the control group (p value = 0.010). The score of patient satisfaction concerning the procedure before the POEM in the carbonated beverage group was 4.5 ± 0.652 , while the score in the control group was 4.35 ± 0.702 (p value = 0.436). In the multivariate analysis, patient satisfaction was significantly associated with male (odds ratio 0.296, 95% CI: 0.097-0.905, p value = 0.033). Conclusions. Drinking carbonated beverages reduce the duration of preoperative endoscopy and ameliorate the esophagus cleansing degrees without impairing patient satisfaction. [ABSTRACT FROM AUTHOR]