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The impact of COVID-19 vaccination on clinical outcomes in solid organ transplant (SOT) recipients remains unclear. This systematic review and network meta-analysis sought to assess the efficacy and safety of COVID-19 vaccination in SOT recipients. We searched 6 databases from inception to March 1, 2024 for randomized controlled trials (RCTs) and observational studies evaluating different COVID-19 vaccination strategies in SOT recipients. Based on patient-important outcomes, we performed frequentist random-effects pairwise meta-analyses and network meta-analyses, separating RCTs and nonrandomized evidence, and used the Grading of Recommendation, Assessment, Development, and Evaluation approach to assess our certainty in the evidence. We included 6 RCTs (N = 814) and 43 observational studies (N = 125 199). Overall, there is a paucity of randomized evidence evaluating COVID-19 vaccines in SOT recipients. The nonrandomized evidence evaluating COVID-19 vaccination strategies patient-important outcomes, including COVID-19 infection, mortality, hospitalization, ICU admission, and rejection, demonstrated low to very low certainty due to the included studies' risk of bias. Throughout the COVID-19 pandemic, clinicians and SOT recipients worked with minimal, very low-quality evidence in relation to COVID-19 vaccines in this population. In the instance of future public health emergencies, clinicians and researchers should collaborate closely with patient partners to ensure there is sufficient evidence in the transplant population on patient-important outcomes., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and study aims Although outcomes of lumen-apposing metal stents (LAMS) placement in native anatomy have been reported, data on LAMS placement in surgically altered anatomy (SAA) are sparse. We aimed to assess outcomes of LAMS placement in patients with SAA for different indications. Patients and methods This was an international, multicenter, retrospective, observational study at 25 tertiary care centers through November 2023. Consecutive patients with SAA who underwent LAMS placement were included. The primary outcome was technical success defined as correct placement of LAMS. Secondary outcomes were clinical success and safety. Results Two hundred and seventy patients (125 males; average age 61 ± 15 years) underwent LAMS placement with SAA. Procedures included EUS-directed transgastric ERCP (EDGE) and EUS-directed transenteric ERCP (EDEE) (n = 82), EUS-guided entero-enterostomy (n = 81), EUS-guided biliary drainage (n = 57), EUS-guided drainage of peri-pancreatic fluid collections (n = 48), and EUS-guided pancreaticogastrostomy (n = 2). Most cases utilized AXIOS stents (n = 255) compared with SPAXUS stents (n = 15). Overall, technical success was 98%, clinical success was 97%, and the adverse event (AE) rate was 12%. Using AGREE classification, five events were rated as Grade II, 21 events as Grade IIIa, and six events as IIIb. No difference in AEs were noted among stent types ( P = 0.52). Conclusions This study shows that placement of LAMS is associated with high technical and clinical success rates in patients with SAA. However, the rate of AEs is noteworthy, and thus, these procedures should be performed by expert endoscopists at tertiary centers., Competing Interests: Conflict of Interest Benedetto Mangiavillano has no conflict of interest regarding this paper but is consultant for Taewoong medical., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

With the increasing demand for food foaming, how to enhance the foaming properties of protein has gradually become the research focus. This work studied the effect of synephrine (SY) on foaming properties, structure properties, and physicochemical properties of soybean protein isolate (SPI). When the mass ratio of SY to SPI was 1:2, compared with SPI alone, the foam capacity and foam stability of the SY-SPI complex were significantly enhanced. Optical microscopy and confocal laser scanning microscope showed that the improvement in foaming performance was mainly due to the reduction of bubble size and uniform protein distribution. Circular dichroism spectrum and fluorescence spectra indicated that the hydrogen bond of SPI was destroyed and blue shifted with the addition of SY. What's more, the absolute value of Zeta potential, solubility, and hydrophobicity all increased, while the particle size decreased. As a result of molecular docking, surface hydrogen bonds, Van der Waals forces and hydrophobic interactions are the main driving forces. The addition of SY and SPI improved the specific volume and texture of angel cake. This study shows that SY has the potential to be developed into a new type of blowing agent., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Adult patients with biliary acute pancreatitis (BAP) or choledocholithiasis who do not undergo cholecystectomy on index admission have worse outcomes. Given the paucity of data on the impact of cholecystectomy during index hospitalization in children, we examined readmission rates among pediatric patients with BAP or choledocholithiasis who underwent index cholecystectomy versus those who did not., Methods: Retrospective study of children (< 18 years old) admitted with BAP, without infection or necrosis (ICD-10 K85.10), or choledocholithiasis (K80.3x-K80.7x) using the 2018 National Readmission Database (NRD). Exclusion criteria were necrotizing pancreatitis with or without infected necrosis and death during index admission. Multivariable logistic regression was performed to identify factors associated with 30-day readmission., Results: In 2018, 1122 children were admitted for index BAP (n = 377, 33.6%) or choledocholithiasis (n = 745, 66.4%). Mean age at admission was 13 (SD 4.2) years; most patients were female (n = 792, 70.6%). Index cholecystectomy was performed in 663 (59.1%) of cases. Thirty-day readmission rate was 10.9% in patients who underwent cholecystectomy during that index admission and 48.8% in those who did not (p < 0.001). In multivariable analysis, patients who underwent index cholecystectomy had lower odds of 30-day readmission than those who did not (OR 0.16, 95% CI 0.11-0.24, p < 0.001)., Conclusions: Index cholecystectomy was performed in only 59% of pediatric patients admitted with BAP or choledocholithiasis but was associated with 84% decreased odds of readmission within 30 days. Current guidelines should be updated to reflect these findings, and future studies should evaluate barriers to index cholecystectomy., (© 2024. The Author(s).)

Background: Studies suggest that telemedicine worsens health care disparities in certain groups, partly owing to a lack of access to appropriate technology or poor technological literacy. Our aim was to use clinic no-show data to determine the impact of telemedicine on patient access to care in the ambulatory gastroenterology setting. Methods: Single-center retrospective study of ambulatory in-person and telemedicine clinic appointments comparing the 15-month prepandemic (PP) with the first 15 months during the pandemic (DTP) using an administrative database. Statistical analysis was performed using univariate and multivariable logistic regression. Results: About 9,746 and 12,808 patient-encounters were scheduled PP and DTP respectively. The no-show rate decreased from 9.8% to 6.9% DTP (p < 0.001). The no-show rate decreased for Black (p = 0.02) and non-Hispanic White patients (p = 0.018). The no-show rate increased for LatinX (p < 0.001) and Asian ( p  = 0.007) patients. In multivariate analysis, older patients and patients identifying as Black, Asian, or LatinX all had higher odds of no-show DTP (p < 0.05 for all). Patients from high-income counties were 43% less likely to no-show than those in the lowest income counties. Conclusions: The transition to telemedicine improves health care access by decreasing the overall no-show rate. Some groups have been negatively affected, including the older, lower income, LatinX, and Asian populations. Future studies should aim to identify the risk factors within these populations that can be modified to increase health care participation, including targeted application of in-person visits, and improved technology to drive engagement.

Background: Adult patients with cholecystitis who do not undergo cholecystectomy on index admission have worse outcomes, however, there is a paucity of data of the role of cholecystectomy during index hospitalization in the pediatric population. Our aim was to determine outcomes and readmission rates among pediatric patients with cholecystitis who underwent index cholecystectomy versus those who did not., Methods: We performed a retrospective study of pediatric (< 18 years old) admitted with acute cholecystitis (AC) requiring hospitalization using the 2018 National Readmission Database (NRD). Exclusion criteria included age ≥ 18 years and death on index admission. Multivariable logistic regression was performed to identify factors associated with 30-day readmissions., Results: We identified 550 unique index acute cholecystitis admissions. Mean age was 14.6 ± 3.0 years. Majority of patients were female (n = 372, 67.6%). Index cholecystectomy was performed in (n = 435, 79.1%) of cases. Thirty-day readmission rate was 2.8% in patients who underwent index cholecystectomy and 22.6% in those who did not (p < 0.001). On multivariable analysis, patients who did not undergo index cholecystectomy had higher odds of 30-day readmission than those who did not (OR 10.66, 95% CI 5.06-22.45, p < 0.001). Female patients also had higher odds of 30-day readmission compared to males (OR 3.37, 95% CI 1.31-8.69)., Conclusions: Patients who did not undergo index cholecystectomy had over tenfold increase in odds of 30-day readmission. Further research is required to understand the barriers to index cholecystectomy despite society recommendations and clear clinical benefit., (© 2023. The Author(s).)

Aims: Neutrophils play a pivotal in immunity and inflammation. We aim to investigate the prevalence of neutropenia in the United States., Methods: In this cross-sectional study, participants from the National Health and Nutrition Examination Survey (NHANES) (2011-2018) were enrolled. Demographic information, hematologic measurements, smoking status of all participants were collected for all participants. All statistical analyses were performed utilizing the NHANES survey weights. Covariate-adjusted linear regression was used to compare hematologic indices in different population grouped by age, sex, ethnicity, and smoking. We also employed multivariate-logistic regression to estimate the weighted odds ratio with a 95% confidence interval and predict the neutropenia risk among., Results: 32,102 participants from NHANES survey were included, represented 286.6 million multiracial population in the United States. Black participants had lower mean leukocyte count (mean difference (MD): 0.71 × 10 9 /L; P < 0.001) and lower neutrophil count (MD: 0.83 × 10 9 /L; P < 0.001) compared with white participants after adjusting for age and sex. Furthermore, t a notable observation was the significant downward shift in the distribution curves of leukocyte count and neutrophil count among black participants. Smokers had a higher mean leukocyte count (MD: 1.10 × 10 9 cells/L; P < 0.001) and a higher mean neutrophil count (MD: 0.75 × 10 9 cells/L; P < 0.001) comparing with nonsmokers. The estimated prevalence of neutropenia was 1.24% (95% CI: 1.11 - 1.37%), which corresponds to approximately 35.5 million individuals in the United States. The prevalence of neutropenia in black participants was significantly higher than other races. Results of logistic regression analysis showed that black individuals, male individuals, and children younger than 5 years had a higher risk of neutropenia., Conclusions: Neutropenia is more common in the general population than we thought, especially in black individuals and children. More attention should be paid to neutropenia., (© 2023. The Author(s).)

Background and study aims Endoscopist techniques affect biliary cannulation success and the risk of adverse events during endoscopic retrograde cholangiopancreatography (ERCP). This survey study aims to understand the current practice of biliary cannulation techniques among endoscopists. Methods Practicing endoscopists were sent an anonymous 28-question electronic survey on biliary cannulation techniques and intraprocedural pancreatitis prophylactic strategies. Results The survey was completed by 692 endoscopists (6.2% females). A wire-guided cannulation technique (WGT) was the preferred initial biliary cannulation approach (95%). The preferred secondary approaches were a double-wire (DWT) (65.8%), precut needle-knife technique (NKT) (25.7%), transpancreatic sphincterotomy (5.9%) or other (2.6%). Overall, 18.1% of respondents were not comfortable with NKTs. In the setting of pancreatic duct (PD) access, 81.9% and 97% reported a threshold of three or more wire passes or contrast injections into the PD, respectively, before changing strategy, 34% reported placement of a prophylactic PD stent <50% of the time and 12.1% reported removal of the PD stent at the end of the procedure. Advanced endoscopy fellowship (AEF) training and high volume (>200 ERCPs per year) were associated with comfort with precut NKTs and likelihood of prophylactic PD stent ( P <0.001 for both). Conclusions A WGT technique followed by the DWT and NKT were the preferred biliary cannulation techniques; however, almost one-fifth of respondents were not comfortable with the NKT. There was considerable variability in secondary cannulation approaches, time spent attempting biliary cannulation and prophylactic PD stent placement, factors known to be associated with cannulation success and adverse outcomes., Competing Interests: Conflict of Interest Mustafa A. Arain: Consultant for Olympus and Boston Scientific. Muhammad K. Hasan: Consultant for Olympus and Boston Scientific. All other authors have no conflicts of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background and Aims: Over-The-Scope Clips (OTSC) use have shown promising results for first line treatment of non-variceal upper gastrointestinal bleeding (NVUGIB). We conducted this meta-analysis to compare outcomes in patients treated with OTSC versus standard endoscopic intervention for first line endoscopic treatment of NVUGIB., Methods: We reviewed several databases from inception to December 9, 2022 to identify studies comparing OTSC and standard treatments as the first line treatment for NVUGIB. The outcomes assessed included re-bleeding, initial hemostasis, need for vascular embolization, mortality, need for repeat endoscopy, 30 day readmission rate, and need for surgery. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using random effect model. Heterogeneity was assessed by I 2 statistic., Results: We included 11 studies with 1608 patients (494 patients in OTSC group and 1114 patients in control group). OTSC use was associated with significantly lower risk of re-bleeding (RR, 0.58; 95% CI 0.41-0.82). We found no significant difference in rates of initial hemostasis (RR, 1.05; 95% CI 0.99- 1.11), vascular embolization rates (RR, 0.93; 95% CI 0.40- 2.13), need for repeat endoscopy (RR, 0.78; 95% CI 0.40-1.49), 30 day readmission rate (RR, 0.59; 95% CI 0.17-2.01), need for surgery (RR, 0.81; 95% CI 0.29-2.28) and morality (RR, 0.69; 95% CI 0.38-1.23)., Conclusions: OTSC are associated with significantly lower risk of re-bleeding compared to standard endoscopic treatments when used as first line endoscopic therapy for NVUGIB., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Rapid on-site-evaluation (ROSE) with an in-room cytopathologist (ROSE-P) has been shown to improve the diagnostic yield of specimens obtained from patients undergoing EUS-guided FNA or fine-needle biopsy sampling (EUS-FNAB) of pancreatic lesions. Recently, there has been an increased interest and use of ROSE using telecytology (ROSE-T) to optimize clinical workflows and to address social distancing mandates created during the coronavirus disease 2019 pandemic. The purpose of this study was to compare diagnostic outcomes of ROSE-P and ROSE-T., Methods: A single-center cohort study of patients who underwent EUS-FNAB of solid pancreatic lesions with ROSE was conducted. The primary outcome was overall diagnostic yield of cancer. All patients who underwent EUS-FNAB were entered into a prospectively maintained database. Statistical analyses were performed using descriptive statistics and univariate analysis., Results: There were 165 patients in each arm. There was no difference in diagnostic yield between ROSE-P and ROSE-T (96.4% vs 94.5%, P = .428). ROSE-T was associated with an increased use of 22-gauge needles (P = .006) and more needle passes (P < .001). No significant differences were found in age, gender, lesion size, needle type, procedure times, or adverse events between the 2 groups (P < .05 for all). More pancreatic tail lesions were sampled in the ROSE-P group (P < .001)., Conclusions: ROSE-T was not associated with any difference in final histologic diagnosis for EUS-FNAB of solid pancreatic masses. This has important implications for optimizing clinical workflows., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: ERCP is the first line of treatment for benign and malignant biliary obstruction and EUS-guided biliary drainage (EUS-BD) is usually used for patients who have failed ERCP. Recently, several studies have evaluated the role of EUS-BD in the management of benign biliary obstruction. This meta-analysis evaluates the efficacy and safety of EUS-BD in the management of benign biliary obstruction., Methods: We reviewed several databases from inception to July 8, 2022, to identify studies evaluating the efficacy and safety of EUS-BD in the management of benign biliary obstruction. Our outcomes of interest were technical success, clinical success, and adverse events. Pooled rates with 95% confidence intervals (CIs) for all outcomes were calculated using a random effects model. Subgroup analyses were performed including patients with normal anatomy versus surgically altered anatomy (SAA). Heterogeneity was assessed by I 2 statistic., Results: We included 14 studies with 329 patients. The pooled rate (95% CI) of technical success was 88% (83%, 92%). The pooled rate (95% CI) of technical success for patients with SAA and normal anatomy was 92% (85%, 96%) and 83% (75%, 89%), respectively. The pooled rates (95% CI) of clinical success and adverse events were 89% (83%, 93%) and 19% (13%, 26%), respectively. We found low heterogeneity in most of the analyses., Conclusions: EUS-BD is an effective and safe option in patients with benign biliary obstruction and should be considered after a failed attempt at ERCP or when ERCP is not technically possible., Competing Interests: None

Aims: We aim to investigate the association of the Dietary Inflammatory Index (DII) with the prevalence of hypertension in a large multiracial population in the United States., Methods: Participants from the National Health and Nutrition Examination Survey (NHANES) (1999-2018) were included in this cross-sectional study. Dietary information was obtained and used to calculate DII. Blood pressures of participants were measured by experienced examiners. The NHANES used the method of "stratified multistage probability sampling," and this study is a weight analysis following the NHANES analytic guidance. Weight logistic regression analysis was adopted to investigate the association of hypertension with DII. Least Absolute Shrinkage and Selection Operator (LASSO) regression was carried out to screen the most important dietary factors associated with the risk of hypertension. Moreover, a nomogram model based on key dietary factors was established; the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic power of the nomogram model for screening hypertension risk., Results: A total of 45,023 participants were included in this study, representing 191 million residents in the United States. Participants with hypertension had an elevated DII compared with those without hypertension. Weight logistic regression showed that an increment of DII was strongly associated with hypertension after adjusting for confounding factors. The nomogram model, based on key dietary factors screened by LASSO regression, showed a favorable discriminatory power with an area under the curve (AUC) of 78.5% (95% CI: 78.5%-79.3%). Results of the sensitivity analysis excluding participants who received any drug treatment were consistent with those in the main analysis., Conclusion: An increment of DII is associated with the risk of hypertension. For better prevention and treatment of hypertension, more attention should be paid to controlling dietary inflammation., 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 © 2023 Zhou, Xie, Liu, Xu, Dai, Lu, Weng and Wu.)

ERCP is the first line of treatment for malignant biliary obstruction and EUS-guided biliary drainage (EUS-BD) is usually used for patients who have failed ERCP. EUS-guided gallbladder drainage (EUS-GBD) has been suggested as a rescue treatment for patients who fail EUS-BD and ERCP. In this meta-analysis, we have evaluated the efficacy and safety of EUS-GBD as a rescue treatment of malignant biliary obstruction after failed ERCP and EUS-BD. We reviewed several databases from inception to August 27, 2021, to identify studies that evaluated the efficacy and/or safety of EUS-GBD as a rescue treatment in the management of malignant biliary obstruction after failed ERCP and EUS-BD. Our outcomes of interest were clinical success, adverse events, technical success, stent dysfunction requiring intervention, and difference in mean pre- and postprocedure bilirubin. We calculated pooled rates with 95% confidence intervals (CI) for categorical variables and standardized mean difference (SMD) with 95% CI for continuous variables. We analyzed data using a random-effects model. We included five studies with 104 patients. Pooled rates (95% CI) of clinical success and adverse events were 85% (76%, 91%) and 13% (7%, 21%). Pooled rate (95% CI) for stent dysfunction requiring intervention was 9% (4%, 21%). The postprocedure mean bilirubin was significantly lower compared to preprocedure bilirubin, SMD (95% CI): -1.12 (-1.62--0.61). EUS-GBD is a safe and effective option to achieve biliary drainage after unsuccessful ERCP and EUS-BD in patients with malignant biliary obstruction., Competing Interests: None

Background and study aims  A second examination of the right colon, either as a second forward view (SFV) or as retroflexion (RF) in the cecum, can increase adenoma detection rate (ADR) in the right colon. In this meta-analysis, we have evaluated the role of a second examination of the right colon in improving ADR. Methods  We reviewed several databases to identify randomized controlled trials that compared right colon SFV with no SFV, and RCTs that compared SFV with RF in the right colon, and reported data on ADR. Our outcomes of interest were ADR and polyp detection rate (PDR) with SFV vs no SFV, right colon and total withdrawal times, and additional ADR and PDR with SFV vs RF. For categorical variables, we calculated pooled risk ratios (RRs) with 95 % confidence intervals (CIs); for continuous variables, we calculated standardized mean difference (SMD) with 95 % CI. Data were analyzed using random effects model. Results  We included six studies with 3901 patients. Comparing SFV with no SFV, right colon ADR and PDR were significantly higher in the SFV group: ADR (RR [95 % CI] 1.39 [1.22,1.58]) and PDR (RR [95 % CI] 1.47 [1.30, 1.65]). We found no significant difference in right colon withdrawal time (SMD [95 % CI] 1.54 [-0.20,3.28]) or total withdrawal time (SMD (95 % CI) 0.37 [-0.39,1.13]) with and without SFV. We found no significant difference in additional ADR between SFV and RF. Conclusions  SFV of the right colon significantly increases right-sided and overall ADR., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Polymeric poly(vinyl alcohol) (PVA)-based composite hydrogels are promising materials with various biomedical applications. However, their mechanical and tribological properties should be tailored for such applications. In this study, we report the fabrication of PVA-gellan gum (GG) composite hydrogels and determine the effect of GG content on their rheological and tribological properties. The rheology tests revealed an enhanced storage (elastic) modulus with increased gellan gum (GG) concentration. The results showed up to 89% enhancement of the elastic modulus of PVA by adding 0.5 wt% gellan gum. This elastic modulus (12.1 ± 0.8 kPa) was very close to that of chondrocyte and its surrounding pericellular matrix (12 ± 1 kPa), rendering them ideal for cartilage regeneration applications. Furthermore, the friction coefficient was reduced by up to 80% by adding GG to PVA, demonstrating the increased elastic modulus improved chance of survival under mechanical shear stresses. Examining PVA/GG at different concentrations of 0.1, 0.3, and 0.5 wt% of GG, we demonstrate that at a load of 5 N, the friction coefficient decreases by increasing the GG concentration. However, at higher loads of 10 and 15 N, a 0.3 wt% concentration was sufficient to significantly reduce the friction coefficient. For PVA and PVA/GG composites, we observed a reduction in friction coefficient by increasing the load from 5 to 15 N. We also found the friction to be independent of the sliding velocity. Possible mechanisms of achieving a reduced friction coefficient are discussed.

In recent years, more and more attention had been paid to the combination of proteins and flavonoids, and several flavonoids had been reported to improve the physicochemical and emulsifying properties of proteins. This study investigated the effects of ultrasonic treatment (450 W for 10 min, 20 min, and 30 min) on the physicochemical properties, antioxidant activity, and emulsifying properties of soy protein isolate (SPI) -hawthorn flavonoids (HF) non-covalent complexes. The results showed that the addition of HF to SPI and 20 min of ultrasound could reduce α-helix and random coil, increase β-sheet and β-turn, and enhance fluorescence quenching. In addition, it decreased the particle size, zeta potential, surface hydrophobicity, and turbidity to 88.43 or 95.27 nm, -28.80 mV, 1250.42, and 0.23, respectively. The protein solubility, free sulfhydryl group, antioxidant activity, emulsifying activity index, and emulsifying stability index all increased to 73.93%, 15.07 μmol/g, 71.00 or 41.91%, 9.81 m 2 /g, and 67.71%, respectively. Moreover, high-density small and low-flocculation droplets were formed. Therefore, the combined ultrasound treatment and addition of HF to SPI is a more effective method for protein modification compared to ultrasound treatment alone. It provides a theoretical basis for protein processing and application in the future., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Several studies have examined the efficacy of gastric peroral endoscopic myotomy (G-POEM) for gastroparesis., Aim: To evaluate the mid-term efficacy of G-POEM by meta-analysis of studies with a minimum 1 year of follow-up., Methods: We reviewed several databases from inception to 10 June 2021 to identify studies that evaluated the efficacy of G-POEM in refractory gastroparesis, and had at least 1 year of follow-up. Our outcomes of interest were clinical success at 1 year, adverse events, difference in mean pre- and 1 year post-procedure Gastroparesis Cardinal Symptom Index (GCSI) score, and difference in mean pre- and post-procedure EndoFLIP measurements. We analysed data using a random-effects model and assessed heterogeneity by I 2 statistic., Results: We included 10 studies comprising 482 patients. Pooled rates (95% CI) of clinical success at 1 year and adverse events were 61% (49%, 71%) and 8% (6%, 11%), respectively. Mean GCSI at 1 year post-procedure was significantly lower than pre-procedure; mean difference (MD) (95% CI) -1.4 (-1.9, -0.9). Mean post-procedure distensibility index was significantly higher than pre-procedure in the clinical success group at 40 and 50 mL volume distension; standardised mean difference (95% CI) 0.82 (0.07, 1.64) and 0.91 (0.32, 1.49), respectively. In the clinical failure group, there was no significant difference between mean pre- and post-procedure EndoFLIP measurements., Conclusions: G-POEM is associated with modest clinical success at 1 year. Additional studies with longer follow-up are required to evaluate its longer-term efficacy., (© 2021 John Wiley & Sons Ltd.)

Introduction: Postoperative pain management is an essential module for perioperative care, especially for enhanced recovery after surgery programs. Continuous wound infiltration (CWI) with local anesthetic may be a promising postoperative analgesic strategy. However, its analgesic efficacy and safety remain debatable., Methods: Embase and PubMed databases were systematically searched for relevant randomized controlled trials (RCTs). RCTs assessing the analgesic efficacy and safety of CWI with local anesthetic for postoperative analgesia were selected. The outcomes contained pain scores during rest and mobilization, total opioid consumption, time to the first request of rescue analgesia, length of hospital stay, satisfaction with analgesia, time to return of bowel function, postoperative nausea and vomiting, total complication, wound infection, hypotension, and pruritus. The weighted mean difference and risk ratio were used to pool continuous and dichotomous variables, respectively., Results: A total of 121 RCTs were included. CWI with local anesthetic reduced postoperative pain during rest and mobilization at different time points, increased satisfaction with analgesia, shortened recovery of bowel function, and reduced postoperative nausea and vomiting compared with the placebo group, especially for laparotomy surgery. There were no significant differences in these clinical outcomes compared to epidural and intravenous analgesia. CWI with local anesthetic reduced the total opioid consumption and hypotension risk and did not increase total complications, wound infection, or pruritus. CWI with local anesthetic had a better analgesic efficacy without increased side effects for sternotomy surgery. However, CWI with local anesthetic did not translate into favorable analgesic benefits in laparoscopic surgery., Conclusion: CWI with local anesthetic is an effective postoperative analgesic strategy with good safety profiles in laparotomy and sternotomy surgery, and thus CWI with local anesthetic may be a promising analgesic option enhancing recovery after surgery programs for these surgeries.

Introduction: A step-up endoscopic or percutaneous approach improves outcomes in necrotizing pancreatitis (NP). However, these require multiple radiographic studies and fluoroscopic procedures, which use low-dose ionizing radiation. The cumulative radiation exposure for treatment of NP has not been well defined., Methods: We conducted a retrospective study of consecutive patients with NP admitted to University of California San Francisco Medical Center from January 2011 to June 2019. We calculated effective doses for fluoroscopic procedures using the dose area product and used the National Cancer Institute tool for computed tomography studies. The primary outcome was the cumulative effective dose (CED). Multivariable logistic regression was used to evaluate risk factors of high exposure (CED > 500 mSv)., Results: One hundred seventy-one patients with NP (mean follow-up 40 ± 18 months) underwent a median of 7 (interquartile range [IQR] 5-11) computed tomography scans and 7 (IQR 5-12) fluoroscopic procedures. The median CED was 274 mSv (IQR 177-245) and 30% (51) of patients received high exposure. Risk factors of high exposure include multiorgan failure (aOR 3.47, 95%-CI: 1.53-9.88, P = 0.003), infected necrosis (adjusted odds ratio [aOR] 3.89 95%-CI:1.53-9.88, P = 0.005), and step-up endoscopic approach (aOR 1.86, 95%-CI: 1.41-1.84, P = 0.001) when compared with step-up percutaneous approach., Discussion: Patients with NP were exposed to a substantial amount of ionizing radiation (257 mSv) as a part of their treatment, and 30% received more than 500 mSv, which corresponds with a 5% increase in lifetime cancer risk. Severity of NP and a step-up endoscopic approach were associated with CED > 500 mSv. Further studies are needed to help develop low-radiation treatment protocols for NP, particularly in patients receiving endoscopic therapy., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Human myeloid angiogenic cells (MACs), also termed early endothelial progenitor cells, play an important role in neovascularization and vascular repair. MicroRNAs (miRNAs) are a class of naturally occurring, noncoding, short (∼22 nucleotides), single-stranded RNAs that regulate gene expression post-transcriptionally. MiRNAs have been shown to regulate MAC function. A miRNA signature of MACs was described approximately a decade ago, and many new miRNAs have been discovered in recent years. In this study, we aimed to provide an up-to-date miRNA signature for human MACs. MACs were obtained by culture of human peripheral blood mononuclear cells in endothelial medium for 7 days. Using qPCR array analysis we identified 72 highly expressed miRNAs ( C T value < 30) in human MACs. RT-qPCR quantification of select miRNAs revealed a strong correlation between the C T values detected by the array analysis and RT-qPCR, suggesting the miRNA signature generated by the qPCR array assay is accurate and reliable. Experimentally validated target genes of the 10 most highly expressed miRNAs were retrieved. Only a few of the targets and their respective miRNAs have been studied for their role in MAC biology. Our study therefore provides a valuable repository of miRNAs for future exploration of miRNA function in MACs.

Bronchogenic cysts belong in the category of foregut duplication cysts, along with esophageal and neuroenteric duplication cysts. They are often found incidentally on cross-sectional imaging. Although they are benign, patients often undergo surgical resection because of diagnostic uncertainties. We report the first case of bronchogenic cyst diagnosed with the microforceps, after previous nondiagnostic fine-needle aspirations, thus allowing the patient to avoid surgery., (© 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background and Aims: The American Society for Gastrointestinal Endoscopy recommends prophylactic pancreatic duct stent placement (PPS) and rectal nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce the incidence and severity of post-ERCP pancreatitis (PEP) in high-risk individuals and suggests that rectal indomethacin may decrease the risk and severity of PEP in average-risk individuals. The European Society for Gastrointestinal Endoscopy recommends rectal indomethacin for all patients undergoing ERCP. Previous surveys of European endoscopists revealed low adoption of PPS or rectal NSAIDs to prevent PEP. We sought to capture current practice in the prevention of PEP among endoscopists in the United States involved in advanced endoscopy fellowship programs., Methods: An anonymous online 16-item survey was e-mailed to 233 advanced endoscopists involved in advanced endoscopy fellowship programs., Results: Of the 233 endoscopists who were invited to participate, 62 responded (26.7%). Most respondents reported working in tertiary referral centers (57; 95.0%) and performing ERCP for greater than 5 years (44; 74.6%). All respondents (60; 100.0%) reported working with fellows. Most PPS users (41; 72.0%) reported use of PPS in high-risk patients only and using PPS for PEP in ≤25% of ERCPs (38; 64.4%). Most respondents reported using rectal NSAIDs for high-risk patients only (34; 59.7%) compared with respondents (23; 40.1%) who reported using rectal NSAIDs for prevention of PEP in average-risk patients undergoing ERCP. Most respondents (49; 83.0%) also reported using rapid intravenous fluids to prevent PEP., Conclusions: Among endoscopists involved in advanced endoscopy fellowships in the United States, rectal NSAIDs are used more frequently than PPS in the prevention of PEP. Despite mounting evidence supporting the use of rectal NSAIDs to prevent PEP in average-risk patients, less than half of the respondents in this survey reported such practice., (Copyright © 2020. Published by Elsevier Inc.)

MicroRNAs (miRNAs) regulate a wide range of cellular processes and functions. Blood mononuclear cells (BMNCs) participate in the immune response, inflammatory reaction and angiogenesis. In 2010, a total of 157 miRNAs were quantified by RT-qPCR and a miRNA signature was determined for human peripheral BMNCs. With the advent of technologies such as RNA sequencing, many new miRNAs have been identified. This study was designed to provide an up-to-date miRNA signature for human BMNCs. Peripheral BMNCs were isolated by Ficoll density gradient centrifugation. Using the qPCR array assay, we identified 108 highly expressed miRNAs (Ct value < 30) in human BMNCs. Further validation of the array results by quantifying select miRNAs with RT-qPCR revealed a strong correlation between Ct values derived from array analysis and RT-qPCR, suggesting the array results presented in this study are accurate and reliable. Of note, the function of the majority of the highly expressed miRNAs we have identified has not yet been studied. Our findings may help direct further studies of the regulatory roles of miRNAs in BMNC function.

Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disorder inherited in an autosomal dominant manner. Patients with HHT can develop vascular dysplasias called telangiectasias and arteriovenous malformations (AVMs). Our objective was to profile and characterize micro-RNAs (miRNAs), short noncoding RNAs that regulate gene expression posttranscriptionally, in HHT patient-derived peripheral blood mononuclear cells (PBMCs). PBMCs, comprised mostly of lymphocytes and monocytes, have been reported to be dysfunctional in HHT. A total of 40 clinically confirmed HHT patients and 22 controls were enrolled in this study. PBMCs were isolated from 16 mL of peripheral blood and purified for total RNA. MiRNA expression profiling was conducted with a human miRNA array analysis. Select dysregulated miRNAs and miRNA targets were validated with reverse transcription-quantitative polymerase chain reaction. Of the 377 miRNAs screened, 41 dysregulated miRNAs were identified. Both miR-28-5p and miR-361-3p, known to target insulin-like growth factor 1 (IGF1), a potent angiogenic growth factor, were found to be significantly downregulated in HHT patients. Consequently, IGF1 mRNA levels were found to be significantly elevated. Our research successfully identified miRNA dysregulation and elevated IGF1 mRNA levels in PBMCs from HHT patients. This novel discovery represents a potential pathogenic mechanism that could be targeted to alleviate clinical manifestations of HHT.

Purpose: Argon plasma coagulation (APC) is a standard modality for the treatment of gastrointestinal bleeding. However, there are no metrics to assess technical proficiency. We aimed to determine if a Quick APC Training Test (QAPCTT) can improve performance and assess proficiency with this modality., Materials and Methods: Endoscopy trainees at various levels of training were asked to perform the QAPCTT with an in vivo model before and after an APC curriculum with didactic lectures and additional hands-on experience. As trainees performed the test, endoscopic supervisors recorded the time required to complete each task as well as the number of inadvertent mucosal touchdowns. Each partipant was assigned a technical proficiency score by supervising endoscopists., Results: Fourteen adult gastroenterology fellows participated in the course. 100% of fellows were comfortable with generator settings and APC equipment after the course compared to only 21% (p < 0.001) on the pre-test questionnaire. Those deemed technically proficient on the post-course QAPCTT required significantly less time for the task of making a square (100 s vs. 215 s; p = 0.006) and had significantly fewer inadvertent mucosal touchdowns (5 vs. 19; p = 0.0017)., Conclusions: Dedicated APC training is required to achieve competence with this modality. A structured curriculum improves knowledge about the technique and hands-on training is important for achieving technical proficiency. The QAPCTT appears improve APC technique and may readily identify trainees in need of additional APC experience to gain proficiency., (Copyright © 2018 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Diabetes mellitus (DM) is a chronic, multifactorial metabolic disease whereby insulin deficiency or resistance results in hyperglycemia. Endothelial cells (ECs) form the innermost layer of the blood vessel and produce and release a variety of vasoactive substances and growth factors to regulate vascular homeostasis and angiogenesis. Hyperglycemia and insulin resistance can cause endothelial dysfunction, leading to vascular complications such as coronary artery disease, peripheral arterial disease, diabetic nephropathy, neuropathy and retinopathy. The detrimental effect exerted on ECs by hyperglycemia and insulin resistance underlines the importance of reparatory mechanisms in DM. Endothelial progenitor cells (EPCs), derived from bone marrow, have been recognized as endogenous cells involved in endothelial repair and new blood vessel formation. Initially isolated from a subset of circulating CD34+ mononuclear cells, EPCs were found to possess the ability to differentiate into ECs when cultured in vitro and incorporate into newly formed vessels upon transplantation in animal models of ischemia. Due to the low frequency of CD34+ cells in circulation, the vast majority of studies investigating EPC actions have used cells that are generated through the culture of peripheral blood mononuclear cells (PBMNCs) for 4 - 7 days in endothelial selective medium. These cells, mainly of myeloid hematopoietic cell origin, were termed "Early EPCs," of which, few expressed stem/progenitor-cell markers. Therefore, early EPCs were also termed "myeloid angiogenic cells" (MACs). When PBMNCs are cultured for over 2 weeks, early EPCs gradually diminish while so-called late EPCs appear. Late EPCs share phenotypic features with mature ECs and are therefore also termed blood-derived ECs; they will not be addressed in this review. MAC dysfunction has been observed in a variety of disease conditions including DM. In this article we review the activities and therapeutic potential of MACs in DM. We will interchangeably use "EPCs" and "MACs" to refer to the cells procured by culture of PBMNCs in EC selective medium for approximately 7 days., Competing Interests: None.

Introduction: Orthotopic liver transplantation anastomotic biliary strictures (OLT ABS) are managed with endoscopic biliary stent therapy but the recurrence rate is substantial. Our aims were to retrospectively determine the recurrence rates of OLT ABS after initial successful stent therapy, characterize the management of recurrences and identify associated variables., Materials and Methods: Clinical data from 943 patients receiving non-living donor OLT at our institution from 2005-2012 were reviewed, and 123 OLT ABS patients receiving stent therapy were identified. Features of their endoscopic stent therapy and other pertinent clinical information were evaluated., Results: ABS recurred in 25.5% of patients (24/94) after an initial successful course of stent therapy. Recurrences were received a second course of endoscopic stent therapy and 67% of patients (16/24) achieved long-term remediation of ABS. Six patients underwent a third course of endoscopic stent therapy with 4 patients achieving remediation. Overall remediation rate among ABS recurrences was 83.3% (20/24). A bivariate comparison demonstrated HCV infection, age, median months of maximal stenting and a lower maximum cumulative stent diameter were risk factors for ABS recurrence. Using a Cox regression model, only HCV status proved to be a risk factor for recurrence., Discussion: In conclusion repeat stent therapy achieved high stricture remediation rates. Recurrence after the first or even second course of stenting should not imply failure of endoscopic therapy. A positive HCV status may be associated with higher stricture recurrence rates and this association should be further investigated.

Background: The triple-negative breast cancer (TNBC) is an aggressive cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Preoperative mammography and ultrasound features of TNBC may potentially suggest characteristics of the disease and assist in treatment decisions., Materials and Methods: The study covered 153 patients with TNBC from May 2011 to May 2012 who were confirmed by postoperative pathology results in our hospital. We compared the radiological findings among the patients and sought to determine the significant iconographic features. The biomarkers p53 and Ki-67 are regarded as significant factors in TNBC. They were therefore used to divide the TNBC into four groups for assessment of relationships with TNBC imaging features., Results: On mammography, most TNBCs exhibit obscure (44.3%) masses. On ultrasound, the majority of masses (95.4%) were predominantly indistinct (50.7%), irregular (76.0%) or featuring posterior echo enhancement/shadowing. Color Doppler flow imaging (CDFI) emphasized hypervascular (32.9%) masses. Differences in CDFI by ultrasound among the four groups were statistically significant (p=0.009). There were obvious differences in the percentages of spiculated margin (p=0.049) and intensive posterior echo (p=0.006) with spotty flow imaging by ultrasound between the Ki-67 (+) p53 (+) and other groups., Conclusions: A combination of mammography and ultrasound revealed the imaging characteristics of TNBC included an obscure mass with less attenuated posterior echoes and some vascularity. A worse prognosis was associated with spiculated margin and intensive posterior echoes with spotty flow imaging.

Background: A growing number of studies seem to suggest that small intestinal bacterial overgrowth (SIBO) is a common clinical problem. Although various techniques are available to make this diagnosis, tradition has accepted small bowel aspirate (>10(5) cfu/ml) as a gold standard. In this systematic review, the validity of culture and other diagnostic testing for SIBO is evaluated., Methods: We performed a systematic review of the literature from 1966 to present using electronic databases (PubMed and OVID). Full paper review of those abstracts that fulfilled preset criteria was carried out to evaluate the validity of various tests in diagnosing SIBO. Finally, all papers were evaluated against published standards for studies on diagnostic testing., Results: Seventy-one papers met the criteria for detailed review. Studies were very heterogeneous with regards to patient populations, test definitions, sample size, and methods in general. Small bowel colony counts appeared elevated in most gastrointestinal diseases compared to controls. The traditional definition of >10(5) cfu/ml was usually indicative of stagnant loop conditions. Although, numerous diagnostic tests were studied, not even culture papers met the quality standards described by Reid et al. Breath testing and other diagnostic testing suffered therefore from the lack of a gold standard against which to validate in addition to the poor quality., Conclusions: There is no validated diagnostic test or gold standard for SIBO. In this context, the most practical method to evaluate SIBO in studies at this time would be a test, treat, and outcome technique.

Both the protein kinase C (alpha/beta) inhibitor Go6976 and expression of dominant-negative nuclear factor (NF)-kappaB inhibitor kinase mutants: (a) blocked the growth and caused regression of a mammary tumor insyngeneic mice; (b) inhibited epidermal growth factor (EGF)-induced activation, nuclear translocation, and DNA-binding activity of NF-kappaB; and (c) caused apoptosis of EGF-stimulated cultured mammary tumor cells. cDNA microarray analysis revealed that these treatments reversed the expression changes of a subset of genes altered by EGF treatment. These included: up-regulation of proapoptotic genes of the tumor necrosis factor (TNF) pathway, death-associated protein (DAP) kinase, p53, and p21/Waf1; and down-regulation of inhibitors of apoptosis: inhibitor of apoptosis(IAP)-1 and X-IAP, TNF receptor-associated factor (TRAF)-2, and factors OX40 and 4-1BB. These results and our previous studies suggest the practicality of a target-directed chemotherapy for EGF-responsive breast cancers, by blocking NF-kappaB activation and thereby reinstating apoptosis.

The effect of a kinase inhibitor Go6796 on growth of epidermal growth factor (EGF)-stimulated estrogen receptor negative (ER-) breast cancer cells in vivo and role of nuclear factor kappa B (NF-kappaB) on tumorogenesis have been investigated. This was studied in an animal model by implanting ER- mouse mammary epithelial tumor cells (CSMLO) in syngeneic A-J mice. (i) Local administration of Go6976 an inhibitor of protein kinases C alpha and beta inhibited growth of tumors and caused extensive necrotic degeneration and regression of the tumors without causing any microscopically detectable damage to the vital organs liver and lung. (ii) Stable expression of dominant-negative mutants of the beta subunit (dnIkkbeta) of the inhibitory kappa B (IkappaB) kinase (dnIkk) that selectively blocked activation of NF-kappaB caused loss of tumorigenic potential of CSMLO cells. Stable expression of dnIkkbeta also blocked phorbol 12-myristate 13-acetate (PMA)-induced activation of NF-kappaB and overexpression of cyclin D1, concomitantly with the loss or reduced tumorigenic potential of these cells. Thus, results from in vivo and in vitro experiments strongly suggest the involvement of NF-kappaB in ER- mammary epithelial cell-mediated tumorigenesis. We propose that blocking NF-kappaB activation not only inhibits cell proliferation, but also antagonizes the antiapoptotic role of this transcription factor in ER- breast cancer cells. Thus, NF-kappaB is a potential target for therapy of EGFR family receptor-overexpressing ER- breast cancers.

Purpose: To examine the physiological effects of betaxolol, a beta1-adrenergic receptor blocker commonly used in the treatment of glaucoma, on retinal ganglion cells and to evaluate its potential to elicit responses consistent with a neuroprotective agent against ganglion cell degeneration., Methods: Single-unit extracellular recording, electroretinogram (ERG), intracellular and whole-cell patch-clamp recording techniques were made from flatmounted, isolated retina, superfused eyecup, and living retinal slice preparations of the larval tiger salamander., Results: Bath application of 20 microM betaxolol reduced the glutamate-induced increase of spontaneous spike rate in retinal ganglion cell by approximately 30%. The glutamate-induced postsynaptic current recorded under voltage-clamp conditions was reduced by 50 microM betaxolol, and the difference current-voltage (I-V) relation (I(Control)-I(betaxolol)) was N-shaped and AP5-sensitive, characteristic of N-methyl-D-aspartate receptor-mediated current. Application of 50 microM betaxolol reversibly reduced the voltage-gated sodium and calcium currents by approximately one third of their peak amplitudes. The times-to-action of betaxolol on ganglion cells are long (15-35 minutes for 20-50 microM betaxolol), indicative of modulation through slow biochemical cascades. Betaxolol, up to 100 microM, exerted no effects on horizontal cells or the ERG, suggesting that the primary actions of this beta1 blocker are restricted to retinal ganglion cells., Conclusions: These physiological experiments provide supporting evidence that betaxolol acts in a manner consistent with preventing retinal ganglion cell death induced by elevated extracellular glutamate or by increased spontaneous spike rates under pathologic conditions. The physiological actions of betaxolol lead to reducing neurotoxic effects in ganglion cells, which are the most susceptible retinal neurons to glutamate-induced damages under ischemic and glaucomatous conditions. Therefore, betaxolol has the potential to be a neuroprotective agent against retinal degeneration in patients with disorders mediated by such mechanisms.

Motor proteins of the kinesin superfamily transport intracellular cargo along microtubules. Although different kinesin proteins share 30-50% amino-acid identity in their motor catalytic cores, some move to the plus end of microtubules whereas others travel in the opposite direction. Crystal structures of the catalytic cores of conventional kinesin (a plus-end-directed motor involved in organelle transport) and ncd (a minus-end-directed motor involved in chromosome segregation) are nearly identical; therefore, the structural basis for their opposite directions of movement is unknown. Here we show that the ncd 'neck' made up of 13 class-specific residues next to the superfamily-conserved catalytic core, is essential for minus-end-directed motility, as mutagenesis of these neck residues reverses the direction of ncd motion. By solving the 2.5 A structure of a functional ncd dimer, we show that the ncd neck (a coiled-coil) differs from the corresponding region in the kinesin neck (an interrupted beta-strand), although both necks interact with similar elements in the catalytic cores. The distinct neck architectures also confer different symmetries to the ncd and kinesin dimers and position these motors with appropriate directional bias on the microtubule.

A phosphorylation-initiated mechanism of local protein refolding activates yeast glycogen phosphorylase (GP). Refolding of the phosphorylated amino-terminus was shown to create a hydrophobic cluster that wedges into the subunit interface of the enzyme to trigger activation. The phosphorylated threonine is buried in the allosteric site. The mechanism implicates glucose 6-phosphate, the allosteric inhibitor, in facilitating dephosphorylation by dislodging the buried covalent phosphate through binding competition. Thus, protein phosphorylation-dephosphorylation may also be controlled through regulation of the accessibility of the phosphorylation site to kinases and phosphatases. In mammalian glycogen phosphorylase, phosphorylation occurs at a distinct locus. The corresponding allosteric site binds a ligand activator, adenosine monophosphate, which triggers activation by a mechanism analogous to that of phosphorylation in the yeast enzyme.