An Optimized Ensemble Deep Learning Model for Predicting Plant miRNA-IncRNA Based on Artificial Gorilla Troops Algorithm.

MicroRNAs (miRNA) are small, non-coding regulatory molecules whose effective alteration might result in abnormal gene manifestation in the downstream pathway of their target. miRNA gene variants can impact miRNA transcription, maturation, or target selectivity, impairing their usefulness in plant growth and stress responses. Simple Sequence Repeat (SSR) based on miRNA is a newly introduced functional marker that has recently been used in plant breeding. MicroRNA and long non-coding RNA (lncRNA) are two examples of non-coding RNA (ncRNA) that play a vital role in controlling the biological processes of animals and plants. According to recent studies, the major objective for decoding their functional activities is predicting the relationship between lncRNA and miRNA. Traditional feature-based classification systems' prediction accuracy and reliability are frequently harmed because of the small data size, human factors' limits, and huge quantity of noise. This paper proposes an optimized deep learning model built with Independently Recurrent Neural Networks (IndRNNs) and Convolutional Neural Networks (CNNs) to predict the interaction in plants between lncRNA and miRNA. The deep learning ensemble model automatically investigates the function characteristics of genetic sequences. The proposed model's main advantage is the enhanced accuracy in plant miRNA-IncRNA prediction due to optimal hyperparameter tuning, which is performed by the artificial Gorilla Troops Algorithm and the proposed intelligent preying algorithm. IndRNN is adapted to derive the representation of learned sequence dependencies and sequence features by overcoming the inaccuracies of natural factors in traditional feature architecture. Working with large-scale data, the suggested model outperforms the current deep learning model and shallow machine learning, notably for extended sequences, according to the findings of the experiments, where we obtained an accuracy of 97.7% in the proposed method.

Peroral endoscopic myotomy: anterior versus posterior approach: a randomized single-blinded clinical trial.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) has become the mainstay for the treatment of achalasia at many institutions around the world since its inception in 2008. POEM can be performed using either the anterior or posterior approach. The primary aim of this study was to compare the efficacy of the anterior and posterior approaches at 1 year after POEM. METHODS: This is a single-blinded, randomized, noninferiority international clinical trial. Eligible participants were adult patients with a confirmed diagnosis of achalasia via high-resolution esophageal manometry. Patients were randomly allocated with a 1:1 ratio to receive POEM with anterior or posterior approach. The primary aim was to compare the rate of clinical success (Eckardt score <3) of anterior and posterior approaches at 1 year. RESULTS: One hundred fifty patients were randomized to receive either anterior (n = 73) or posterior (n = 77) POEM. One hundred forty-eight patients received the POEM treatment, and 138 patients completed the 1-year follow-up and were included in the primary efficacy analysis. Technical success was achieved in 71 patients (97.3%) in the anterior group versus 77 patients (100%) in the posterior group (P = .23). The median (interquartile range) length of hospital stay after the procedure was 2 (1-3) days for both groups. Adverse events occurred in 15 patients (10%), 8 patients (11%) in the anterior group and 7 patients (9%) in the posterior group (P = .703). Clinical success was achieved in 90% of patients in the anterior group and 89% of patients in the posterior group. Abnormal esophageal acid exposure was detected in 29 of 59 patients (49%) and 25 of 60 patients (42%) in the anterior and posterior groups, respectively (P = .67). GERD questionnaire scores were also not significantly different between the study groups. In both groups, quality of life improved after POEM for all 36-Item Short-Form Health Survey measures and was similar between both groups. CONCLUSIONS: Posterior myotomy during POEM was not inferior to anterior myotomy in terms of efficacy and safety in the treatment of patients with achalasia. (Clinical trial registration number: NCT02454335.).

An international multicenter study evaluating the clinical efficacy and safety of per-oral endoscopic myotomy in octogenarians.

BACKGROUND AND AIMS: Per-oral endoscopic myotomy (POEM) for achalasia is particularly appealing in the elderly because it is minimally invasive. However, data in patients aged ≥80 years are scarce. The aim of this study was to assess the clinical outcome of POEM in octogenarians. METHODS: This was a multicenter retrospective study at 8 centers. Consecutive octogenarians with achalasia who underwent POEM between 2010 and 2016 were included. Rates of technical success (completion of myotomy), clinical response (Eckardt score ≤3), and adverse events (severity graded as per American Society for Gastrointestinal Endoscopy lexicon) were assessed. RESULTS: A total of 76 patients (47.4% female, mean age 84 years) underwent POEM for treatment of achalasia: type I, 17.1%; type II, 35.5%; type III, 17.1%; and unspecified, 30.3%. Overall, 41.1% were treatment naïve, whereas others had previous botulinum toxin injection and/or pneumatic dilation. The mean (± standard deviation [SD]) age-adjusted Charlson comorbidity index score was 6.2 ± 2.4, with the majority of patients having American Society of Anesthesiologists Physical Status Classification System (ASA) scores of II/III. Technical success was 93.4%, with a median follow-up of 256 days. Fourteen adverse events occurred in 11 patients (14.5%). There were 3 inadvertent mucosotomies, 6 cases of symptomatic capnoperitoneum and/or capnomediastinum, 2 esophageal leaks, 1 cardiac arrhythmia, and 2 other). The severities of these adverse events were mild (78.6%), moderate (14.3%), and severe (7.1%). Clinical success was achieved in 90.8% of patients, with a mean (± SD) Eckardt score reduction from 7.0 ± 2.3 to 0.8 ± 0.1 (P < .001), a median follow-up of 256 days, and interquartile range of 66 to 547. CONCLUSION: Although the rate of technical success may be somewhat lower and the rate of adverse events slightly higher than previously reported, our data suggest that POEM in octogenarians is safe and effective, supporting its role as a primary modality for achalasia in this patient population.

Retraction notice to "Long-term outcomes of per-oral endoscopic myotomy in patients with achalasia with a minimum follow-up of 2 years: an international multicenter study": [YMGE 85 (2017) 927-933].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted due to overlapping/duplicate material. Data from some patients from this study have previously been published in other journals without cross-referencing. Twenty patients overlap with a paper by Kumbhari et al.1 Thirty-five patients overlap with the study by Ngamruengphong et al.2.

Similar Efficacies of Endoscopic Ultrasound Gallbladder Drainage With a Lumen-Apposing Metal Stent Versus Percutaneous Transhepatic Gallbladder Drainage for Acute Cholecystitis.

BACKGROUND & AIMS: Acute cholecystitis in patients who are not candidates for surgery is often managed with percutaneous transhepatic gallbladder drainage (PT-GBD). Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) with a lumen-apposing metal stent (LAMS) is an effective alternative to PT-GBD. We compared the technical success of EUS-GBD versus PT-GBD, and patient outcomes, numbers of adverse events (AEs), length of hospital stay, pain scores, and repeat interventions. METHODS: We performed a retrospective study to compare EUS-GBD versus PT-GBD at 7 centers (5 in the United States, 1 in Europe, and 1 in Asia), from 2013 through 2015, in management of acute cholecystitis in patients who are not candidates for surgery. A total of 90 patients (56 men) with acute cholecystitis (61 calculous, 29 acalculous) underwent EUS-GBD (n = 45) or PT-GBD (n = 45). Data were collected on technical success, clinical success (resolution of symptoms or laboratory and/or radiologic abnormalities within 3 days of intervention), and need for repeat intervention. Characteristics were compared using Student t tests for continuous variables and the chi-square test, or the Fisher exact test, when appropriate, for categorical variables. Adverse events were graded according to American Society for Gastrointestinal Endoscopy definitions and compared using the Fisher exact test. Postprocedure pain scores were compared using the Mann-Whitney U test. RESULTS: Baseline characteristics, type, and clinical severity of cholecystitis were comparable between groups. In the EUS-GBD group, noncautery LAMS were used in 30 patients and cautery-enhanced LAMS were used in 15. Technical success was achieved for 98% of patients in the EUS-GBD and 100% of the patients in the PT-GBD group (P = .88). Clinical success was achieved by 96% of patients in the EUS-GBD group and 91% in the PT-GBD group (P = .20). There was a nonsignificant trend toward fewer AEs in the EUS-GBD group (5 patients; 11%) than in the PT-GBD group (14 patients; 32%) (P = .065). There were no significant differences in the severity of the AEs: mild, 2 in the EUS-GBD group versus 5 in the PT-GBD group (P = .27); moderate, 4 versus 3 (P = .98); severe, 1 versus 3 (P = .62); or deaths, 1 versus 3 (P = .61). The mean postprocedure pain score was lower in the EUS-GBD group than in the PT-GBD group (2.5 vs 6.5; P < .05). The EUS-GBD group had a shorter average length of stay in the hospital (3 days) than the PT-GBD group (9 days) (P < .05) and fewer repeat interventions (11 vs 112) (P < .05). The average number of repeat interventions per patients was 0.2 ± 0.4 EUS-GBD group versus 2.5 ± 2.8 in the PT-GBD group (P < .05). Median follow-up after drainage was comparable in EUS-GBD group (215 days; range, 1-621 days) versus the PT-GBD group (265 days; range, 1-1638 days). CONCLUSIONS: EUS-GBD has similar technical and clinical success compared with PT-GBD and should be considered an alternative for patients who are not candidates for surgery. Patients who undergo EUS-GBD seem to have shorter hospital stays, lower pain scores, and fewer repeated interventions, with a trend toward fewer AEs. A prospective, comparative study is needed to confirm these results.

Efficacy and Safety of Peroral Endoscopic Myotomy for Treatment of Achalasia After Failed Heller Myotomy.

BACKGROUND & AIMS: In patients with persistent symptoms after Heller myotomy (HM), treatment options include repeat HM, pneumatic dilation, or peroral endoscopic myotomy (POEM). We evaluated the efficacy and safety of POEM in patients with achalasia with prior HM vs without prior HM. METHODS: We conducted a retrospective cohort study of 180 patients with achalasia who underwent POEM at 13 tertiary centers worldwide, from December 2009 through September 2015. Patients were divided into 2 groups: those with prior HM (HM group, exposure; n = 90) and those without prior HM (non-HM group; n = 90). Clinical response was defined by a decrease in Eckardt scores to 3 or less. Adverse events were graded according to criteria set by the American Society for Gastrointestinal Endoscopy. Technical success, clinical success, and rates of adverse events were compared between groups. Patients were followed up for a median of 8.5 months. RESULTS: POEM was technically successful in 98% of patients in the HM group and in 100% of patients in the non-HM group (P = .49). A significantly lower proportion of patients in the HM group had a clinical response to POEM (81%) than in the non-HM group (94%; P = .01). There were no significant differences in rates of adverse events between the groups (8% in the HM group vs 13% in the non-HM group; P = .23). Symptomatic reflux and reflux esophagitis after POEM were comparable between groups. CONCLUSIONS: POEM is safe and effective for patients with achalasia who were not treated successfully by prior HM. Although the rate of clinical success in patients with prior HM is lower than in those without prior HM, the safety profile of POEM is comparable between groups.

Comprehensive Analysis of Adverse Events Associated With Per Oral Endoscopic Myotomy in 1826 Patients: An International Multicenter Study.

OBJECTIVES: The safety of peroral endoscopic myotomy (POEM) is still debated since comprehensive analysis of adverse events (AEs) associated with the procedure in large multicenter cohort studies has not been performed. To study (1) the prevalence of AEs and (2) factors associated with occurrence of AEs in patients undergoing POEM. METHODS: Patients who underwent POEM at 12 tertiary-care centers between 2009 and 2015 were included in this case-control study. Cases were defined by the occurrence of any AE related to the POEM procedure. Control patients were selected for each AE case by matching for age, gender, and disease classification (achalasia type I and II vs. type III/spastic esophageal disorders). RESULTS: A total of 1,826 patients underwent POEM. Overall, 156 AEs occurred in 137 patients (7.5%). A total of 51 (2.8%) inadvertent mucosotomies occurred. Mild, moderate, and severe AEs had a frequency of 116 (6.4%), 31 (1.7%), and 9 (0.5%), respectively. Multivariate analysis demonstrated that sigmoid-type esophagus (odds ratio (OR) 2.28, P=0.05), endoscopist experience <20 cases (OR 1.98, P=0.04), use of a triangular tip knife (OR 3.22, P=0.05), and use of an electrosurgical current different than spray coagulation (OR 3.09, P=0.02) were significantly associated with the occurrence of AEs. CONCLUSIONS: This large study comprehensively assessed the safety of POEM and highly suggests POEM as a relatively safe procedure when performed by experts at tertiary centers with an overall 7.5% prevalence of AEs. Severe AEs are rare. Sigmoid-type esophagus, endoscopist experience, type of knife, and current used can be considered as predictive factors of AE occurrence.

Gastric per-oral endoscopic myotomy for refractory gastroparesis: results from the first multicenter study on endoscopic pyloromyotomy (with video).

BACKGROUND AND AIMS: Gastric per-oral endoscopic myotomy (G-POEM) recently has been reported as minimally invasive therapy for gastroparesis. The aims of this study were to report on the first multicenter experience with G-POEM and to assess the efficacy and safety of this novel procedure for patients with gastroparesis with symptoms refractory to medical therapy. METHODS: All patients with gastroparesis who underwent endoscopic pyloromyotomy (G-POEM) at 5 medical centers were included. Procedures were performed following the same principles as esophageal POEM. Clinical response was defined as improvement in gastroparetic symptoms with absence of recurrent hospitalization. Adverse events were graded according to the American Society for Gastrointestinal Endoscopy lexicon. RESULTS: A total of 30 patients with refractory gastroparesis (11 diabetic, 12 postsurgical, 7 idiopathic) underwent G-POEM. Previous therapies included Botox injection in 12, transpyloric stenting in 3, and PEG with jejunal extension (PEGJ) in 1. Nausea/vomiting were the predominant symptoms in 25 patients. Weight loss was present in 27 patients with an average of 10% loss of body weight. G-POEM was completed successfully in all 30 (100%) patients with a mean procedure time of 72 minutes (range, 35-223 min). The mean myotomy length was 2.6 ± 2.3 cm. The mean length of hospital stay was 3.3 days (range, 1-12 days). Two adverse events occurred in 2 (6.7%) patients, including 1 capnoperitoneum and 1 prepyloric ulcer, rated as mild and severe, respectively. Clinical response was observed in 26 (86%) patients during a median follow-up of 5.5 months. Four patients (2 diabetic, 1 postsurgical, 1 idiopathic cause) did not respond to G-POEM. Repeat gastric emptying scan was obtained in 17 patients, normalized in 8 (47%), and improved in 6 (35%) patients. CONCLUSION: G-POEM is a technically feasible procedure. This small non-randomized study suggests the effectiveness of G-POEM for the treatment of patients with gastroparesis refractory to medical therapy. It concomitantly results in normalization of GES in a significant proportion of treated patients.

An international multicenter study comparing EUS-guided pancreatic duct drainage with enteroscopy-assisted endoscopic retrograde pancreatography after Whipple surgery.

BACKGROUND AND AIMS: Endoscopic management of post-Whipple pancreatic adverse events (AEs) with enteroscopy-assisted endoscopic retrograde pancreatography (e-ERP) is associated with high failure rates. EUS-guided pancreatic duct drainage (EUS-PDD) has shown promising results; however, no comparative data have been done for these 2 modalities. The goal of this study is to compare EUS-PDD with e-ERP in terms of technical success (PDD through dilation/stent), clinical success (improvement/resolution of pancreatic-type symptoms), and AE rates in patients with post-Whipple anatomy. METHODS: This is an international multicenter comparative retrospective study at 7 tertiary centers (2 United States, 2 European, 2 Asian, and 1 South American). All consecutive patients who underwent EUS-PDD or e-ERP between January 2010 and August 2015 were included. RESULTS: In total, 66 patients (mean age, 57 years; 48% women) and 75 procedures were identified with 40 in EUS-PDD and 35 in e-ERP. Technical success was achieved in 92.5% of procedures in the EUS-PDD group compared with 20% of procedures in the e-ERP group (OR, 49.3; P < .001). Clinical success (per patient) was attained in 87.5% of procedures in the EUS-PDD group compared with 23.1% in the e-ERP group (OR, 23.3; P < .001). AEs occurred more commonly in the EUS-PDD group (35% vs 2.9%, P < .001). However, all AEs were rated as mild or moderate. Procedure time and length of stay were not significantly different between the 2 groups. CONCLUSIONS: EUS-PDD is superior to e-ERP in post-Whipple anatomy in terms of efficacy with acceptable safety. As such, EUS-PDD should be considered as a potential first-line treatment in post-pancreaticoduodenectomy anatomy when necessary expertise is available.

Long-term outcomes of per-oral endoscopic myotomy in patients with achalasia with a minimum follow-up of 2 years: an international multicenter study.

BACKGROUND AND AIMS: Per-oral endoscopic myotomy (POEM) has shown promising safety and efficacy in short-term studies. However, long-term follow-up data are very limited. The aims of this study were to assess (1) clinical outcome of patients with a minimum post-POEM follow-up of 2 years and (2) factors associated with long-term clinical failure after POEM. METHODS: A retrospective chart review was performed that included all consecutive patients with achalasia who underwent POEM with a minimum follow-up of 2 years at 10 tertiary-care centers. Clinical response was defined by a decrease in Eckardt score to 3 or lower. RESULTS: A total of 205 patients (45.8% men; mean age, 49 years) were followed for a median of 31 months (interquartile range, 26-38 months). Of these, 81 patients (39.5%) had received previous treatment for achalasia before POEM. Clinical success was achieved in 98% (185/189), 98% (142/144), and 91% (187/205) of patients with follow-up within 6 months, at 12 months, and ≥24 months, respectively. Of 185 patients with clinical response at 6 months, 11 (6%) experienced recurrent symptoms at 2 years. History of previous pneumatic dilation was associated with long-term treatment failure (odds ratio, 3.41; 95% confidence interval, 1.25-9.23). Procedure-related adverse events occurred in 8.2% of patients and only 1 patient required surgical intervention. Abnormal esophageal acid exposure and reflux esophagitis were documented in 37.5% and 18% of patients, respectively. However, these rates are simply a reference number among a very selective group of patients. CONCLUSIONS: POEM is safe and provides high initial clinical success and excellent long-term outcomes. Among patients with confirmed clinical response within 6 months, 6% had recurrent symptoms by 2 years.

Endoscopic ultrasound-guided creation of a transgastric fistula for the management of hepatobiliary disease in patients with Roux-en-Y gastric bypass.

Background and aims Endoscopic retrograde cholangiopancreatography (ERCP) in patients who have undergone Roux-en-Y gastric bypass (RYGB) is technically challenging. We describe our multicenter experience using lumen-apposing metal stents (LAMSs) to create an endoscopic ultrasound-guided transgastric fistula (EUS-TG) to facilitate peroral ERCP in these patients. Patients and methods Thirteen patients with RYGB who underwent EUS-TG at three tertiary centers were included. EUS was used to guide puncture of the excluded stomach from the gastric pouch or jejunum; a LAMS was placed across the transgastric fistula. ERCP was performed via a duodenoscope passed through the LAMS. Results The technical success of EUS-TG was 100 % (13/13). ERCP through the LAMS was successful and clinical success was achieved in all patients. LAMS dislodgement during ERCP occurred in two patients and the stent was successfully repositioned without sequelae. After removal of the LAMS, the fistula was closed in 92 % of patients, either by endoscopic closure devices or argon plasma coagulation. None of the patients experienced procedure-related adverse events. Conclusion EUS-TG is an effective and safe method of accessing the excluded stomach and performing ERCP in patients with RYGB.

Lumen-apposing covered self-expandable metal stents for short benign gastrointestinal strictures: a multicenter study.

Background and study aim Use of the fully covered self-expandable metal stent (SEMS) for benign luminal gastrointestinal (GI) stricture (BLGS) has been limited by the migration rate. The role of the lumen-apposing metal stent (LAMS) for BLGS is not well defined. We assessed the safety, feasibility, and efficacy of LAMS for the treatment of BLGS. Patients and methods This was an observational, open-label, retrospective, single-arm, multicenter consecutive case series of patients undergoing LAMS placement for BLGS. Technical success was defined as successful placement of the LAMS. Short- and long-term clinical success rates were defined as symptom improvement/resolution with indwelling stent and after stent removal, respectively. All adverse events and additional interventions were recorded. Results A total of 30 patients (mean age 51.6 years; 63.3 % women) underwent LAMS placement for GI strictures (83.9 % anastomotic). Median stricture diameter and length were 4.5 mm (range 2 - 10 mm) and 8 mm (range 5 - 10 mm), respectively. Technical success was achieved in 29 patients (96.7 %), with an adverse event rate of 13.3 %. The stent migration rate was 8.0 % (2/25) on follow-up endoscopy. Short-term clinical success was achieved in 90.0 % (27/30) at a median of 60 days (interquartile range [IQR] 40 - 90 days). Most patients (19/23; 82.6 %) experienced sustained symptom improvement/resolution without the need for additional interventions at a median follow-up of 100 days (IQR 60 - 139 days) after LAMS removal. Conclusion This multicenter study demonstrated that LAMS placement represents a safe, feasible, and effective therapeutic option for patients with BLGS and is associated with a low stent migration rate. Our initial findings suggest that future prospective comparative studies are needed on the use of LAMS, endoscopic dilation, and conventional SEMS. .

EUS-guided gastroenterostomy is comparable to enteral stenting with fewer re-interventions in malignant gastric outlet obstruction.

BACKGROUND AND AIMS: Endoscopic enteral stenting (ES) in malignant gastric outlet obstruction (GOO) is limited by high rates of stent obstruction. EUS-guided gastroenterostomy (EUS-GE) is a novel procedure that potentially offers sustained patency without tumor ingrowth/overgrowth. The aim of this study is to compare EUS-GE with ES in terms of (1) symptom recurrence and need for re-intervention, (2) technical success (proper stent positioning as determined via endoscopy and fluoroscopy), (3) clinical success (ability to tolerate oral intake without vomiting), and (4) procedure-related adverse events (AEs). METHODS: Multicenter retrospective study of all consecutive patients who underwent either EUS-GE at four centers between 2013 and 2015 or ES at one center between 2008 and 2010. RESULTS: A total of 82 patients (mean age 66-years ± 13.5 and 40.2% female) were identified: 30 in EUS-GE and 52 in ES. Technical and clinical success was not significantly different: 86.7% EUS-GE versus 94.2% ES (p = 0.2) and 83.3% EUS-GE versus 67.3% ES (p = 0.12), respectively. Symptom recurrence and need for re-intervention, however, was significantly lower in the EUS-GE group (4.0 vs. 28.6%, (p = 0.015). Post-procedure mean length of hospitalization was comparable at 11.3 days ± 6.6 for EUS-GE versus 9.5 days ± 8.3 for ES (p = 0.3). Rates and severity of AEs (as per the ASGE lexicon) were also similar (16.7 vs. 11.5%, p = 0.5). On multivariable analysis, ES was independently associated with need for re-intervention (OR 12.8, p = 0.027). CONCLUSION: EUS-GE may be ideal for malignant GOO with comparable effectiveness and safety to ES while being associated with fewer symptom recurrence and requirements for re-intervention.

Is POEM the Answer for Management of Spastic Esophageal Disorders? A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Spastic esophageal disorders (SEDs) include spastic achalasia (type III), diffuse esophageal spasm (DES), and nutcracker/jackhammer esophagus (JH). Per-oral endoscopic myotomy (POEM) has demonstrated efficacy and safety in the treatment of achalasia. Recently, POEM has been indicated for the treatment of SEDs. We conducted a systematic review and meta-analysis to determine the clinical success and safety of POEM in SEDs. METHODS: We searched several databases from 01/01/2007 to 01/10/2016 to identify studies (with five or more patients) on POEM for the treatment of SEDs. Weighted pooled rates (WPRs) for clinical success and adverse events (AEs) were calculated for all SEDs. Clinical success was defined as Eckardt scores of ≤3 and/or improvement in severity of dysphagia based on achalasia disease-specific health-related quality of life questionnaire. The WPRs for clinical success and AEs were analyzed using fixed- or random-effects model based on heterogeneity. The proportionate difference in clinical success and post-procedure adverse event rates among individual types of SEDs was also calculated. RESULTS: A total of eight observational studies with 179 patients were included in the final analysis. Two studies were of good quality and six were of fair quality based on the National Institutes of Health quality assessment tool. The WPR with 95% confidence interval (CI) for cumulative clinical success of POEM in all SEDs was 87% (78, 93%), I 2 = 37%. The total number of patients for individual disorders, i.e., type III achalasia, JH, and DES, was 116, 37, and 18, respectively. The WPRs for clinical success of POEM for type III achalasia, DES, and JH were 92, 88, and 72%, respectively. Proportion difference of WPR for clinical success was significantly higher for type III achalasia in comparison with JH (20%, P = 0.01). The WPR with 95% CI for AEs of POEM in all SEDs was 14% (9, 20%), I 2 = 0%. The WPRs for post-procedure adverse events for type III achalasia, DES, and JH were 11, 14, and 16%, respectively. There was no difference in safety of POEM among individual SEDs. CONCLUSION: POEM is an effective and safe therapeutic modality for the treatment of spastic esophageal disorders.

Musashi-2 (MSI2) regulation of DNA damage response in lung cancer.

Lung cancer is one of the most common types of cancer worldwide. Non-small cell lung cancer (NSCLC), typically caused by KRAS and TP53 driver mutations, represents the majority of all new lung cancer diagnoses. Overexpression of the RNA-binding protein (RBP) Musashi-2 (MSI2) has been associated with NSCLC progression. To investigate the role of MSI2 in NSCLC development, we compared the tumorigenesis in mice with lung-specific Kras-activating mutation and Trp53 deletion, with and without Msi2 deletion (KPM2 versus KP mice). KPM2 mice showed decreased lung tumorigenesis in comparison with KP mice. In addition, KPM2 lung tumors showed evidence of decreased proliferation, but increased DNA damage, marked by increased levels of phH2AX (S139) and phCHK1 (S345), but decreased total and activated ATM. Using cell lines from KP and KPM2 tumors, and human NSCLC cell lines, we found that MSI2 directly binds ATM mRNA and regulates its translation. MSI2 depletion impaired DNA damage response (DDR) signaling and sensitized human and murine NSCLC cells to treatment with PARP inhibitors in vitro and in vivo. Taken together, we conclude that MSI2 supports NSCLC tumorigenesis, in part, by supporting repair of DNA damage by controlling expression of DDR proteins. These results suggest that targeting MSI2 may be a promising strategy for lung cancers treated with DNA-damaging agents.

Immunosuppression with cyclosporine versus tacrolimus shows distinctive nephrotoxicity profiles within renal compartments.

AIM: Calcineurin inhibitors (CNIs) are the backbone for immunosuppression after solid organ transplantation. Although successful in preventing kidney transplant rejection, their nephrotoxic side effects contribute to allograft injury. Renal parenchymal lesions occur for cyclosporine A (CsA) as well as for the currently favored tacrolimus (Tac). We aimed to study whether chronic CsA and Tac exposures, before reaching irreversible nephrotoxic damage, affect renal compartments differentially and whether related pathogenic mechanisms can be identified. METHODS: CsA and Tac were administered chronically in wild type Wistar rats using osmotic minipumps over 4 weeks. Functional parameters were controlled. Electron microscopy, confocal, and 3D-structured illumination microscopy were used for histopathology. Clinical translatability was tested in human renal biopsies. Standard biochemical, RNA-seq, and proteomic technologies were applied to identify implicated molecular pathways. RESULTS: Both drugs caused significant albeit differential damage in vasculature and nephron. The glomerular filtration barrier was more affected by Tac than by CsA, showing prominent deteriorations in endothelium and podocytes along with impaired VEGF/VEGFR2 signaling and podocyte-specific gene expression. By contrast, proximal tubule epithelia were more severely affected by CsA than by Tac, revealing lysosomal dysfunction, enhanced apoptosis, impaired proteostasis and oxidative stress. Lesion characteristics were confirmed in human renal biopsies. CONCLUSION: We conclude that pathogenetic alterations in the renal compartments are specific for either treatment. Considering translation to the clinical setting, CNI choice should reflect individual risk factors for renal vasculature and tubular epithelia. As a step in this direction, we share protein signatures identified from multiomics with potential pathognomonic relevance.

Subpleural sparing: Clinical, physiological, and radiological implications.

The term "subpleural sparing" refers to computed tomography (CT) images that indicate that there is limited disease/infiltrate in the immediate subpleural location. This observation is often associated with nonspecific interstitial pneumonitis and is a characteristic that distinguishes this pathology from usual interstitial pneumonitis (idiopathic pulmonary fibrosis). Subpleural sparing can also occur in acute respiratory disorders, including pulmonary contusion in children, acute lung disease associated with electronic cigarettes (vaping), and aspiration of exogenous lipids. Potential explanations for this observation include nonuniform distribution of lung injury/inflammation, nonuniform clearing/resolution of injury, and variations in CT image acquisition and presentation. The subpleural region contains lymphatic structures on the interior surface of the visceral pleura and in interlobular septa. The density of subpleural lymphatics decreases in more interior zones of the lung that largely contain alveolar-capillary units. These lymphatics transfer fluid and other inflammatory mediators from the peripheral lung into central lymphatics and veins. Consequently, the density and distribution of lymphatics could explain preferential clearing of the subpleural regions during acute injury. The acquisition of CT images also depends on the configuration of detectors, slice thickness, and the energy of the electron beam. Clinicians should carefully consider the disease process, lymphatic function and other clearance mechanisms, and the vagaries in CT image acquisition when they evaluate patients with subpleural sparing.

Characteristics and outcomes of patients with sepsis who had cortisol level measurements or received hydrocortisone during their intensive care unit management: A retrospective single center study.

Objectives: The current guidelines for managing patients with sepsis include the early cultures, administration of antibiotics, and fluid resuscitation. Several clinical trials have tried to determine whether or not the administration of corticosteroids improves outcomes in these patients. This study analyzed the characteristics of a large group of critically ill patients who either had cortisol levels drawn during their intensive care unit management or had hydrocortisone administered during their management. Methods: A list of patients who had cortisol levels measured or who had hydrocortisone administered empirically for the treatment of sepsis was identified by the medical record department at University Medical Center in Lubbock, Texas. The primary outcome was in-hospital mortality. Secondary outcomes included the need for mechanical ventilation, the need for renal replacement therapy, the need for vasopressors, length of stay, and the development of nosocomial infections. Results: This study included 351 patients, including 194 women (55.3%). The mean age was 62.9 ± 16.1 years. The mean admission SOFA score was 9.3 ± 3.63, the mean APACHE 2 score was 18.15 ± 7.7, and the mean lactic acid level was 3.8 ± 4.0 mmol/L. One hundred sixty-two patients required intubation, 262 required vasopressors, 215 developed acute kidney injury, and 319 had cortisol levels measured. The mean length of stay was 11.5 ± 13.7 days; the mortality rate was 32.2%. Multiple variable analysis demonstrated that higher cortisol levels were associated with increased mortality (44.1% if cortisol ⩾20 µg/dL versus 17.5% if cortisol <20 µg/dL). One hundred forty-five patients received corticosteroids, and multivariable analysis demonstrated that these patients had increased mortality (40.0% versus 26.7%). Conclusion: In this study, higher cortisol levels were associated with increased mortality. The administration of hydrocortisone was associated with increased mortality possibly reflecting the use of this medication in patients who had a higher likelihood of poor outcomes.

Lung Cancer as a Leading Cause among Paraneoplastic Non-Bacterial Thrombotic Endocarditis: A Meta-Analysis of Individual Patients' Data.

Hypercoagulability is strongly associated with cancer and may result in non-bacterial thrombotic endocarditis (NBTE). The aim of our meta-analysis was to explore the demographics and characteristics of this condition in cancer. Databases were systematically searched. The outcomes were to identify the annual trend in premortem diagnosis among the entire cohort and different subgroups and to identify differences in characteristics and survival in the considered population. A total of 121 studies with 144 patients were included. The proportion of marantic endocarditis associated with lung cancer was 0.29 (95% CI, 0.21-0.37; p < 0.001), that associated with pancreatic cancer was 0.19 (95% CI, 0.13-0.27; p < 0.001), that associated with advanced cancer stage (metastasis) was 0.69 (95% CI, 0.61-0.76; p < 0.001), and that associated with adenocarcinoma was 0.65 (95% CI, 0.56-0.72; p < 0.001). Median and 6-month overall survival (OS) were 1.3 months and 32.3%, respectively, with 6-month OS of 20.8% vs. 37.0% in lung vs. other cancers, respectively (p = 0.06) and 42.9% vs. 31.1% among those who underwent intervention vs. those who did not (p = 0.07). Cases discovered in recent years had better survival (HR = 0.98 (95% CI, 0.96-0.99; p = 0.003). While cancer-associated NBTE is a rare entity, lung cancers were the most common tumor site and are frequently associated with more advanced and metastatic cancer stages. The prognosis is dismal, especially among lung cancers.