Real-world study of palbociclib combined with endocrine therapy for patients with metastatic breast cancer: A comparison of subsequent treatment patterns and HER2 expression analysis.

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy (ET) comprise the standard treatment for patients with hormone receptor-positive and human epidermal growth factor 2 (HER2)-negative metastatic breast cancer. The optimal systematic treatment after progression on palbociclib and the role of HER2 expression among these patients remain unclear. METHODS: The authors retrospectively identified 361 patients who received palbociclib combined with ET. Progression-free survival (PFS) and overall survival (OS) were analyzed based on subsequent treatments and HER2 status (PFSsub and OSsub, respectively). PFS1 and OS1 were calculated from palbociclib administration to disease progression/death and death from any cause, respectively. PFSsub and OSsub were calculated from subsequent treatment initiation. RESULTS: The median PFS1 and OS1 were 10.2 and 39.9 months, respectively. The median PFSsub and OSsub of 111 patients (54.7%) who received chemotherapy were 4.9 months and 20.0 months, respectively, whereas those of 89 patients (43.8%) who received endocrine backbone therapy were 5.9 months and 29.3 months, respectively. Among them, 31 patients (15.3%) who received abemaciclib combined with new ET showed better PFSsub and OSsub (12.2 months and not reached, respectively). The median PFS1 was significantly shorter in the HER2-low subgroup than in the HER2-zero subgroup among patients who received second-line or later palbociclib (6.1 vs. 7.8 months; p = .040) but did not differ among patients who received first-line palbociclib. CONCLUSIONS: Various regimens after palbociclib use were received. An improvement was noted in PFS among patients who received endocrine backbone therapy relative to chemotherapy, which may have been secondary to the receipt of chemotherapy by patients with more aggressive disease. HER2 status was not related to the effect of first-line palbociclib, but it may play a role in later lines.

Single-cell RNA-seq analysis decodes the kidney microenvironment induced by polystyrene microplastics in mice receiving a high-fat diet.

In recent years, the environmental health issue of microplastics has aroused an increasingly significant concern. Some studies suggested that exposure to polystyrene microplastics (PS-MPs) may lead to renal inflammation and oxidative stress in animals. However, little is known about the essential effects of PS-MPs with high-fat diet (HFD) on renal development and microenvironment. In this study, we provided the single-cell transcriptomic landscape of the kidney microenvironment induced by PS-MPs and HFD in mouse models by unbiased single-cell RNA sequencing (scRNA-seq). The kidney injury cell atlases in mice were evaluated after continued PS-MPs exposure, or HFD treated for 35 days. Results showed that PS-MPs plus HFD treatment aggravated the kidney injury and profibrotic microenvironment, reshaping mouse kidney cellular components. First, we found that PS-MPs plus HFD treatment acted on extracellular matrix organization of renal epithelial cells, specifically the proximal and distal convoluted tubule cells, to inhibit renal development and induce ROS-driven carcinogenesis. Second, PS-MPs plus HFD treatment induced activated PI3K-Akt, MAPK, and IL-17 signaling pathways in endothelial cells. Besides, PS-MPs plus HFD treatment markedly increased the proportions of CD8+ effector T cells and proliferating T cells. Notably, mononuclear phagocytes exhibited substantial remodeling and enriched in oxidative phosphorylation and chemical carcinogenesis pathways after PS-MPs plus HFD treatment, typified by alterations tissue-resident M2-like PF4+ macrophages. Multispectral immunofluorescence and immunohistochemistry identified PF4+ macrophages in clear cell renal cell carcinoma (ccRCC) and adjacent normal tissues, indicating that activate PF4+ macrophages might regulate the profibrotic and pro-tumorigenic microenvironment after renal injury. In conclusion, this study first systematically revealed molecular variation of renal cells and immune cells in mice kidney microenvironment induced by PS-MPs and HFD with the scRNA-seq approach, which provided a molecular basis for decoding the effects of PS-MPs on genitourinary injury and understanding their potential profibrotic and carcinogenesis in mammals.

Comparative analysis of codon usage patterns in the chloroplast genomes of nine forage legumes.

Leguminosae is one of the three largest families of angiosperms after Compositae and Orchidaceae. It is widely distributed and grows in a variety of environments, including plains, mountains, deserts, forests, grasslands, and even waters where almost all legumes can be found. It is one of the most important sources of starch, protein and oil in the food of mankind and also an important source of high-quality forage material for animals, which has important economic significance. In our study, the codon usage patterns and variation sources of the chloroplast genome of nine important forage legumes were systematically analyzed. Meanwhile, we also constructed a phylogenetic tree based on the whole chloroplast genomes and protein coding sequences of these nine forage legumes. Our results showed that the chloroplast genomes of nine forage legumes end with A/T bases, and seven identical high-frequency (HF) codons were detected among the nine forage legumes. ENC-GC3s mapping, PR2 analysis, and neutral analysis showed that the codon bias of nine forage legumes was influenced by many factors, among which natural selection was the main influencing factor. The codon usage frequency showed that the Nicotiana tabacum and Saccharomyces cerevisiae can be considered as receptors for the exogenous expression of chloroplast genes of these nine forage legumes. The phylogenetic relationships of the chloroplast genomes and protein coding genes were highly similar, and the nine forage legumes were divided into three major clades. Among the clades Melilotus officinalis was more closely related to Medicago sativa, and Galega officinalis was more closely related to Galega orientalis. This study provides a scientific basis for the molecular markers research, species identification and phylogenetic studies of forage legumes. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01421-0.

[Randomized,double-blind,parallel controlled,multicenter clinical trial of effectiveness and safety of Shexiang Zhuifeng Zhitong Ointment in alleviating pain in knee osteoarthritis(syndrome of cold-dampness obstruction)].

The Shexiang Zhuifeng Zhitong Ointment with the effects of dispelling wind, removing dampness, dissipating cold, and relieving pain is used for treating arthralgia, muscular pain, and sprain pain caused by cold-dampness obstruction. To evaluate the efficacy and safety of Shexiang Zhuifeng Zhitong Ointment in relieving the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction), a randomized, double-blind, parallel controlled, multicenter clinical trial was conducted. The stratified randomization method was used to randomize the 240 subjects into a treatment group and a control group in a ratio of 1∶1. In each group, 60 patients received external application for 12 h and the other 60 patients received external application for 6 h. The treatment group received external application of Shexiang Zhuifeng Zhitong Ointment, while the control group received external application of Shexiang Zhuifeng Ointment. The treatment lasted for 21 days in both groups. Follow-up was conducted on days 7, 14, and 21 of treatment. The results based on the full analysis set were as follows.(1)In visual analog scale(VAS) score, the mean difference in the VAS score between baseline and 12 h post-treatment was 3.02 in the treatment group and 2.31 in the control group, with a significant difference(P<0.05). The mean difference in the VAS score between baseline and 6 h post-treatment was 3.19 in the treatment group and 2.48 in the control group, with a significant difference(P<0.05).(2)Response rate in terms of VAS score, after treatment for 12 h, the response rate was 93.22% in the treatment group and 73.33% in the control group, with a significant difference(P<0.05). After treatment for 6 h, theresponse rate in the treatment group was 88.33%, which was higher than that(63.33%) in the control group(P<0.05).The results showed that Shexiang Zhuifeng Zhitong Ointment applied for 12 and 6 h effectively relieved the knee joint pain of patients with knee osteoarthritis due to cold-dampness obstruction, as demonstrated by the reduced VAS score, Western Ontario and McMaster Universities Arthritis Index(WOMAC), stiffness, and joint function score. Moreover, Shexiang Zhuifeng Zhitong Ointment outperformed the positive control Shexiang Zhuifeng Ointment in terms of reducing the VAS score, demonstrating a definitetherapeutic effect on the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction).In addition, Shexiang Zhuifeng Zhitong Ointment did not cause other adverse reactions except for mild allergic reactions, which were common in the external application of traditional Chinese medicine plasters on the skin, inseveral patients.Neither other adverse reactions nor abnormalities of liver and kidney functions and electrocardiogram were observed. This ointment had high safety and could be popularized in clinical application.

Transcutaneous Auricular Vagal Nerve Stimulation Is Effective for the Treatment of Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

INTRODUCTION: Vagal nerve stimulation (VNS) can be used to modulate gastrointestinal motility, inflammation, and nociception. However, it remains unclear whether VNS is effective in adult patients with functional dyspepsia (FD). We investigated the effectiveness of transcutaneous auricular VNS (taVNS) in patients with FD. METHODS: Consecutive patients with FD meeting Rome IV criteria with modified FD Symptom Diary score ≥10 were enrolled. Patients were randomly allocated to 10-Hz taVNS (V10 group), 25-Hz taVNS (V25 group), or sham group, with 30 minutes of treatment twice a day for 4 weeks. The primary outcome was the response rate at week 4, defined as the proportion of patients whose modified FD Symptom Diary score was reduced ≥5 when compared with the baseline. Secondary outcomes included adequate relief rate and adverse events. RESULTS: A total of 300 patients were randomized to V10 (n = 101), V25 (n = 99), and sham groups (n = 100). After 4 weeks of treatment, V10 and V25 groups had a higher response rate (81.2% vs 75.9% vs 47%, both P < 0.001) and adequate relief rate (85.1% vs 80.8% vs 67%, both P < 0.05) compared with the sham group. There was no significant difference between V10 and V25 in response rate and adequate relief rate (both P > 0.05). The efficacy of taVNS (both 10 and 25 Hz) lasted at week 8 and week 12 during follow-up period. Adverse events were all mild and comparable among the 3 groups (1%-3%). DISCUSSION: Our study firstly showed that 4-week taVNS (both 10 and 25 Hz) was effective and safe for the treatment of adult FD ( clinicaltrials.gov number: NCT04668534).

Pre-procedure oral administration of pronase improves efficacy of lugol chromoendoscopy in esophageal squamous cell carcinoma screening: a prospective, double-blinded, randomized, controlled trial.

BACKGROUND AND AIMS: Chromoendoscopy with Lugol's staining is used to screen for early esophageal squamous cell carcinoma (ESCC). Its efficacy is greatly limited by unstandardized defoaming preparation. This study aimed to confirm whether pre-procedure oral administration of pronase could improve the diagnostic performance of Lugol chromoendoscopy in high-risk patients being screened for early ESCC. METHODS: A total of 955 patients at-risk were prospectively recruited for screening for ESCC. Patients were randomly assigned (1:1) to groups with or without (control group) pronase administration. Endoscopic diagnosis of early ESCC was based on the presence of pink-color sign in Lugol's unstained area, and a biopsy was routinely conducted if the Lugol's unstained lesion was larger than 0.5 cm. The early cancer detection rate was used as the primary endpoint. RESULTS: Pre-procedure oral administration of pronase improved mucosal visibility during Lugol chromoendoscopy (P = 0.008). There were no differences in the number of Lugol's unstained lesions between the 2 groups (23.27% [111/477] vs. 25.11% [120/478], P = 0.508). Meaningfully, the detection rate of ESCC (confirmed by histopathology) was significantly higher in the pronase group than in the control group (27.03% [30/111] vs. 17.50% [21/120], P = 0.041), as well as the detection rate of lesions with pink-color sign during chromoendoscopy (35.14% [39/111] vs. 13.33% [16/120], P < 0.001). The diagnostic performance of Lugol chromoendoscopy had improved with the use of pronase (area under the curve = 0.85 vs. 0.69, P = 0.019), accompanied by an increased sensitivity (86.67% vs. 47.62%, P = 0.004). There was no difference in the adverse events between the 2 groups (P = 0.793). CONCLUSIONS: Pre-procedure oral administration of pronase significantly increased the detection rate of early ESCC and optimized the diagnostic performance of Lugol chromoendoscopy, which should be recommended during routine endoscopic screening for early ESCC in high-risk patients. TRIAL REGISTRATION: Pronase improves efficacy of Lugol chromoendoscopy screening on esophageal cancerous lesions (NCT02030769).

Effects of exogenous indole-3-acetic acid on the density of trichomes, expression of artemisinin biosynthetic genes, and artemisinin biosynthesis in Artemisia annua.

Artemisinin is the most practical medication for the treatment of malaria, but is only very minimally synthesized in Artemisia annua, significantly less than the market needs. In this study, indole-3-acetic acid (IAA) was used to investigate its effects on trichomes, artemisinin accumulation, and biosynthetic gene expression in A. anuua. The results showed that exogenous IAA could contribute to the growth and development of A. annua and increase the density of trichomes. Analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that artemisinin and dihydroartemisinic acid (DHAA) contents were increased by 1.9-fold (1.1 mg/g) and 2.1-fold (0.51 mg/g) after IAA treatment in comparison with control lines (CK), respectively. Furthermore, quantitative real-time PCR results showed that AaADS, AaCYP71AV1, AaALDH1, and AaDBR2, four critical enzyme genes for the biosynthesis of artemisinin, had relatively high transcription levels in leaves of A. annua treated with IAA. In summary, this study indicated that exogenous IAA treatment was a feasible strategy to enhance artemisinin production, which paves the way for further metabolic engineering of artemisinin biosynthesis.

Endoscopic Papillary Large Balloon Dilation Reduces Further Recurrence in Patients With Recurrent Common Bile Duct Stones: A Randomized Controlled Trial.

INTRODUCTION: Up to 60% of patients with common bile duct stone (CBDS) recurrence suffer from further recurrence after endoscopic retrograde cholangiopancreatography (ERCP). There are no effective methods to prevent recurrence in most patients. In this study, we aimed to assess the short-term and long-term efficacies of endoscopic papillary large balloon dilation (EPLBD) for the management of recurrent CBDS in a randomized controlled trial. METHODS: Consecutive patients with recurrent CBDS were eligible and randomly assigned in a 1:1 ratio to the EPLBD group or the control group. The primary outcome was the CBDS recurrence rate within 2 years after ERCP. The analysis followed the intention-to-treat principle. RESULTS: From 2014 to 2021, 180 patients with recurrent CBDS were included, with 90 in each group. All patients underwent complete CBDS clearance by 1 or several sessions of ERCP. The rate of complete clearance in 1 session was significantly higher with EPLBD treatment (95.6% vs 85.6%, P = 0.017). During the follow-up, the CBDS recurrence rate within 2 years was significantly lower in the EPLBD group than in the control group (21.1% [19/90] vs 36.7% [33/90], relative risk 0.58, 95% confidence interval 0.36-0.93, P = 0.021). At a median follow-up of approximately 56 months, CBDS recurrence was found in 34.4% of the patients (31/90) in the EPLBD group and 51.1% (46/90) in the control group (hazard ratio 0.57, 95% confidence interval 0.36-0.89, P = 0.012). Multiple recurrences (≥2) were also decreased in the EPLBD group (4.4% vs 18.9%, P = 0.020). DISCUSSION: During the long-term follow-up, nearly half of the patients with recurrent CBDS experienced stone recurrence after traditional ERCP. Our study was the first to show that EPLBD effectively reduced the recurrence of CBDS.

Difficult biliary cannulation in ERCP procedures with or without trainee involvement: a comparative study.

BACKGROUND: The 5-5-1 criteria (> 5 minutes - 5 cannulation attempts - 1 unintended pancreas duct cannulation) were proposed by the European Society of Gastrointestinal Endoscopy to define difficult biliary cannulation. However, the criteria may be inappropriate for trainee-involved procedures. We developed criteria for difficult cannulation in trainee-involved procedures. METHODS: Patients undergoing biliary cannulation with or without trainee involvement were eligible. Procedures that might be too easy (e. g. fistula) or too difficult (e. g. altered anatomy) were excluded. The primary outcome was difficult cannulation, defined as cannulation time, attempts, or inadvertent pancreatic duct (PD) cannulation exceeding the 75 % percentile of each variable. Propensity score matching (PSM) analysis was used. RESULTS: After PSM, there were 1596 patients in each group. Trainee-involved procedures had longer median (interquartile range [IQR]) cannulation time (7.5 [2.2-15.3] vs. 2.0 [0.6-5.2] minutes), and more attempts (5 [2-10] vs. 2 [1-4]) and inadvertent PD cannulation (0 [0-2] vs. 0 [0-1]) vs. procedures without trainee involvement (all P < 0.001). The 15-10-2 criteria for difficult cannulation were proposed for trainee-involved cannulation and the 5-5-1 criteria were nearly confirmed for cannulation without trainee involvement. The proportions of difficult cannulation using these respective criteria were 35.5 % (95 % confidence interval [CI] 33.2 %-37.9 %) and 31.8 % (95 %CI 29.5 %-34.2 %), respectively (odds ratio 1.18 [95 %CI 1.02-1.37]). Incidences of post-ERCP pancreatitis following difficult cannulation were comparable (7.8 % [95 %CI 5.7 %-10.3 %] vs. 9.8 % [95 %CI 7.4 %-12.8 %], respectively). CONCLUSION: By using the 75 % percentiles as cutoffs, the proposed 15-10-2 criteria for difficult cannulation could be appropriate in trainee-involved procedures.

The efficacy and safety of palbociclib combined with endocrine therapy in patients with hormone receptor-positive HER2-negative advanced breast cancer: a multi-center retrospective analysis.

To explore the efficacy and safety of palbociclib combined with endocrine therapy (ET) in advanced breast cancer (ABC). We conducted a retrospective study involving patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) ABC who received palbociclib combined with ET in the first- to third-line at three centers in China between January 2018 and October 2020. A total of 151 patients were included in this study. The median age of the patients at palbociclib initiation was 56 years (range 30-86 years) with a median follow-up of 10.9 months (range 2.0-41.2 months). Among these patients, 88 patients received palbociclib combined with ET as first-line therapy, and achieved a median progression-free survival (mPFS) of 19.8 months and an objective response rate (ORR) of 40.9%, meanwhile, in the first-line setting, 62 patients received palbociclib at an initial dose of 125 mg, achieving a mPFS of 20.9 months and an ORR of 46.8%. There were 39 and 24 patients who received palbociclib combined with ET as second- and third-line therapy, the mPFS were 10.0 months and 6.1 months, respectively. The most common and serious adverse events (AEs) were leukopenia and neutropenia. A total of 64 patients (42.4%) underwent palbociclib dose reduction due to AEs. Palbociclib combined with ET is an effective therapeutic regimen for HR+/HER2- ABC, particularly in the first-line setting with palbociclib initial dose of 125 mg, and AEs were manageable.

Superiority of a preparation-related model for predicting inadequate bowel preparation in patients undergoing colonoscopy: A multicenter prospective study.

BACKGROUND AND AIM: Three models based on patient-related factors have been developed to predict inadequate bowel preparation (BP). However, the performance of the models seems suboptimal. This study aimed to develop a novel preparation-related model and compare it with the available patient-related models. METHODS: Patients receiving standard BP were prospectively enrolled from five endoscopic centers. Patient-related and preparation-related factors for inadequate BP (defined by segmental Boston Bowel Preparation Scale score < 2) were identified by logistic regression. A preparation-related model was derived and internally validated in 906 patients. The comparisons of models were assessed by discrimination and calibration. The preparation-related model was also externally validated. RESULTS: Several patient-related factors (male and American Society of Anesthesiologists Physical Status Classification System score ≥ 3) and preparation-related factors (drinking-to-stool interval ≥ 3 h, preparation-to-colonoscopy interval ≥ 6 h, and poor rectal effluent) were found to be independently associated with inadequate BP (all P < 0.05). C-statistics was 0.81 for the preparation-related model in the training cohort (n = 604), significantly higher than three available patient-based models (0.58-0.61). Similar results were observed in the validation cohort (n = 302). Calibration curves showed close agreement in the preparation-related model (R2  = 0.315 in the training cohort and 0.279 in the validation cohort). The preparation-related model was externally validated in another 606 patients with C-index of 0.80. CONCLUSIONS: A new preparation-related model (consisting of drinking-to-stool interval ≥ 3 h, preparation-to-colonoscopy interval ≥ 6 h, and poor last rectal effluent) was developed and performed better than three available patient-related models. This easy-to-use model may be a useful decision-support tool on individualized plans in patients undergoing BP.

Functional dyspepsia symptom diary is correlated with other questionnaires and associated with severity in patients with functional dyspepsia: a multicenter, prospective observational study.

BACKGROUND AND AIM: Functional dyspepsia symptom diary (FDSD) is a newly designed questionnaire of functional dyspepsia (FD). The relationships between FDSD and other FD-related questionnaires and patient-reported severity remain unclear. This study aims to investigate the correlations between FDSD and other questionnaires and to determine the relationships between FDSD and FD severity. METHODS: Consecutive outpatients with FD were prospectively enrolled in four tertiary hospitals. All patients were evaluated by six FD-related questionnaires, including FDSD, Dyspepsia Symptom Severity Index (DSSI), Gastrointestinal Symptom Rating Scale, Short-Form Nepean Dyspepsia Index, and Hamilton Depression and Anxiety Scale (HAMD and HAMA). The severity of FD was also graded as mild, moderate, and severe by patients themselves. Correlations between different scores were assessed by Spearman correlation coefficient (ρ), and risk factors for patient-reported severity were identified. RESULTS: For 512 enrolled FD patients, the overall median FDSD score was 19 (2-42). FDSD was well correlated with DSSI (ρ = 0.64) and fairly correlated with the other four scores (ρ = 0.32-0.55) (all P < 0.001). Mild, moderate, and severe FD were reported by 18.5%, 55.9%, and 25.6% of patients, respectively. There were seven factors associated with the severe FD, including education level, duration, and subtypes of FD, prior treatment, FDSD, HAMD, and HAMA scores (all P < 0.10). FDSD ≥ 20 (odds ratio [OR] 3.3, 95% confidence interval [CI]: 2.0-5.2, P < 0.001) and HAMD ≥ 13 (OR 2.9, 95% CI: 1.8-4.6, P < 0.001) were independently associated with patient-reported severe FD. CONCLUSIONS: This study firstly revealed that the newly developed FDSD correlated with other FD-related questionnaires. FDSD ≥ 20 and HAMD ≥ 13 were independently associated with severe FD reported by patients (clinicaltrials.gov number: NCT04953975).

Machine Learning Prediction Models for Gestational Diabetes Mellitus: Meta-analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common endocrine metabolic disease, involving a carbohydrate intolerance of variable severity during pregnancy. The incidence of GDM-related complications and adverse pregnancy outcomes has declined, in part, due to early screening. Machine learning (ML) models are increasingly used to identify risk factors and enable the early prediction of GDM. OBJECTIVE: The aim of this study was to perform a meta-analysis and comparison of published prognostic models for predicting the risk of GDM and identify predictors applicable to the models. METHODS: Four reliable electronic databases were searched for studies that developed ML prediction models for GDM in the general population instead of among high-risk groups only. The novel Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess the risk of bias of the ML models. The Meta-DiSc software program (version 1.4) was used to perform the meta-analysis and determination of heterogeneity. To limit the influence of heterogeneity, we also performed sensitivity analyses, a meta-regression, and subgroup analysis. RESULTS: A total of 25 studies that included women older than 18 years without a history of vital disease were analyzed. The pooled area under the receiver operating characteristic curve (AUROC) for ML models predicting GDM was 0.8492; the pooled sensitivity was 0.69 (95% CI 0.68-0.69; P<.001; I2=99.6%) and the pooled specificity was 0.75 (95% CI 0.75-0.75; P<.001; I2=100%). As one of the most commonly employed ML methods, logistic regression achieved an overall pooled AUROC of 0.8151, while non-logistic regression models performed better, with an overall pooled AUROC of 0.8891. Additionally, maternal age, family history of diabetes, BMI, and fasting blood glucose were the four most commonly used features of models established by the various feature selection methods. CONCLUSIONS: Compared to current screening strategies, ML methods are attractive for predicting GDM. To expand their use, the importance of quality assessments and unified diagnostic criteria should be further emphasized.

Combination prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis in patients undergoing double-guidewire assisted biliary cannulation: A case-control study with propensity score matching.

BACKGROUND AND AIM: Rectal indomethacin and pancreatic duct stenting (PDS) are recommended for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). However, the effects of the combination of the two methods on preventing PEP are controversial. We hypothesized that some group of difficult patients might benefit from the combination of indomethacin plus PDS (IP) compared with indomethacin alone (IN). METHODS: Patients with native papilla who underwent endoscopic retrograde cholangiopancreatography in eight tertiary hospitals were screened. They were enrolled if the cannulation proved difficult and post-procedure indomethacin was administered. Propensity score matching (PSM) was used to balance the baseline characteristics between IP and IN groups. The primary outcome was PEP. RESULTS: Among 4456 patients with available cannulation-related data, 1889 (42.4%) patients had difficult cannulation and received indomethacin. After PSM, both IP and IN groups included 332 patients. PEP was comparable between the two groups (12.7% vs 10.2%, P = 0.329). By subgroup analysis, the PEP rate was found to be lower in the IP group than in the IN group (7.3% vs 18.2%, P = 0.026) in patients undergoing double-guidewire technique (DGT). The results of an additional analysis using PSM in DGT patients were consistent with the subgroup analysis results (7.8% vs 19.4%, P = 0.036). CONCLUSIONS: The current study indicated that the combined prevention of PEP with indomethacin plus PDS was useful in PEP prevention in patients undergoing DGT. Other groups of patients with difficult cannulation may not benefit from the combination strategy.

Factors Associated With Adenoma Detection in Propofol-sedated Patients.

GOALS: To assess the factors associated with adenoma detection in propofol-sedated patients. BACKGROUNDS: Low adenoma detection rate (ADR) are linked to increased risk of interval cancer and related deaths. Compared with air insufflation (AI) colonoscopy, the method of water exchange (WE) significantly decreased insertion pain and increased ADR in unsedated patients. Deep sedation with propofol has been increasingly used in colonoscopy. One report suggested that WE significantly increased ADR in propofol-sedated patients, but the factors associated with adenoma detection were not analyzed. STUDY: Post hoc multiple logistic regression analyses were performed based on pooled data from 2 randomized controlled trials to assess the factors associated with adenoma detection in propofol-sedated patients. RESULTS: Propofol-sedated patients (n=510) were randomized to AI and WE. The baseline characteristics were comparable. Multiple logistic regression analyses show that age, withdrawal time, indications (screening vs. diagnostic), and WE were significantly and independently associated with higher ADR. WE had fewer patients with inadequate Boston Bowel Preparation Scale score of <6. Despite a significantly shorter inspection time, WE had significantly higher overall ADR than AI, especially in those with adequate Boston Bowel Preparation Scale of ≥6. Right colon ADR (17.5% vs. 10.5%), flat ADR (32.3% vs. 19.4%), combined advanced and sessile serrated ADR (13.1% vs. 7.4%) of WE were significantly higher than those of AI. CONCLUSIONS: WE enhanced quality of colonoscopy in propofol-sedated patients by significantly improving colon cleanliness and overall ADR. Colonoscopists with patients under propofol sedation might consider evaluating WE method for performance improvement.

Patient-related factors associated with successful cannulation by trainees during hands-on endoscopic retrograde cholangiopancreatography training.

BACKGROUND AND AIM: Hands-on endoscopic retrograde cholangiopancreatography (ERCP) training is essential for trainees to grasp the technique. Cannulation success rate (CSR) is considered one of the main indicators of competency of trainees. We aimed to investigate whether patient-related factors had an impact on the CSR of trainees. METHODS: A post hoc analysis of data from two multicenter studies (NCT02002650 and NCT03057769) was conducted. Patients aged 18-90 years with native papilla undergoing ERCP were eligible for this study. Only procedures involving trainees in centers strictly following "10-min criteria" for initial cannulation were enrolled. Primary outcome was CSR by trainees. RESULTS: From December 2013 to October 2017, 20 trainees in four centers were involved in initial cannulation in 1044 patients with native papilla. Primary CSR by trainees was 61.0% (436/715), 31.5% (70/222) and 44.9% (48/107) in patients with common bile duct stone (CBDS), biliary stricture (BS) and other indications, respectively (P < 0.001). In multivariate analysis, indication of BS (OR, 0.31; 95% CI, 0.22-0.44; P < 0.001) and presence of type A diverticulum (OR, 1.69; 95% CI, 1.23-2.33; P = 0.001) were both independently associated with cannulation success of trainees. Biliary infection was significantly higher in the BS than in the CBDS group (3.6% vs 0.7%, P = 0.004), whereas other post-ERCP complications were comparable between the two groups. CONCLUSIONS: Indication of BS and the presence of type A diverticulum were independently associated with the success of cannulation by trainees. These findings indicate that greater effort is needed for trainees to improve the ability of cannulation in BS.

Same-Day Single Dose of 2 Liter Polyethylene Glycol is Not Inferior to The Standard Bowel Preparation Regimen in Low-Risk Patients: A Randomized, Controlled Trial.

OBJECTIVES: Split dose of 4 l polyethylene glycol (PEG) is currently the standard regimen for bowel preparation (BP). However, it may be unnecessary for patients without high risks (e.g., old age, constipation, and diabetes, and so on) for inadequate BP. The study aimed to compare the efficacy of bowel cleansing between low-risk patients receiving same-day, single dose of low-volume (SSL) PEG vs. standard regimen. METHODS: This prospective, randomized, observer-blinded, non-inferiority study enrolled low-risk patients in three centers. Patients undergoing colonoscopy were randomized (1:1) to the SSL or standard group. The primary outcome was adequate BP, defined by Boston Bowel Preparation Score (BBPS) ≥6 and each segmental score ≥2. Secondary outcomes included adverse events, cecal intubation rate, and patient willingness to repeat BP, and so on. RESULTS: Among 2,532 patients eligible for the study, 940 (37.1%) were at low risk and 792 (31.3%) at high risk for inadequate BP. The low-risk patients were randomly allocated to the SSL (n=470) or standard group (n=470). The baseline characteristics of the two groups were similar. Intention-to-treat analysis showed that adequate BP was achieved in 88.1% in the SSL group and 87.0% in the standard group (relative risk (RR) 1.10, 95% confidence interval (CI): 0.75-1.63, P=0.621). The overall BBPS was 7.3±1.2 and 7.3±1.3, respectively (P=0.948). No significant differences were found between the two groups with regards to the right, transverse, and left-segmental colon BBPS (all P>0.05). However, in terms of adverse events, patients in the SSL group reported less nausea (19.6% vs. 29.9%), vomiting (5.3% vs. 11.4%), and abdominal discomfort (2.2% vs. 6.0%) compared with those in the standard group. More patients in the SSL group were willing to repeat BP (94.0% vs. 89.5%, P=0.015). CONCLUSIONS: For low-risk patients, the SSL regimen was not inferior to the split dose of 4 l PEG for adequacy of BP. Single dose of low-volume regimen had significantly fewer adverse events. This simplified regimen may be preferable in the "easy-to prepare" population.

Water Exchange Method Significantly Improves Adenoma Detection Rate: A Multicenter, Randomized Controlled Trial.

OBJECTIVES: Adenoma detection rate (ADR) is a key colonoscopy quality indicator in Western clinical literature. Our low ADR prompted us to assess novel methods to improve performance. Western retrospective reports suggested that water exchange (WE) could increase ADR. However, most of these studies used pain score or intubation rate as the primary outcome. Here we test the hypothesis that WE significantly increases ADR among Chinese colonoscopists and design a prospective randomized controlled trial using ADR as our primary outcome. METHODS: This prospective, randomized controlled trial was performed at six centers in China. Screening, surveillance, and diagnostic cases were randomized to be examined by WE or traditional air insufflation (AI) method. The primary outcome was ADR. RESULTS: From April 2014 to July 2015, 3,303 patients were randomized to WE (n=1,653) and AI (n=1,650). The baseline characteristics were comparable. Overall ADR was 18.3% (WE) and 13.4% (AI) (relative risk 1.45, 95% confidential interval: 1.20-1.75, P<0.001). ADR in screening patients using AI was 25.8% (male) and 15.7% (female). ADR in screening patients aged >50 years old was 29.4% (WE) and 22.9% (AI) (relative risk 1.09, 95% confidential interval: 1.00-1.19, P=0.040). The increase by WE was reproducibly observed in all indication categories, and significant in screening and diagnostic cases. The limitation imposed by the unblinded investigators was mitigated by comparable inspection times in cases without polyps, similar adenoma per positive colonoscopy, and reproducible enhancement of ADR and adenoma per colonoscopy by WE across all eight investigators. CONCLUSIONS: This prospective study confirms Western retrospective data that WE significantly improves ADR among Chinese colonoscopists. WE may be superior to AI for screening colonoscopy in China. Colonoscopists elsewhere with low ADR might consider evaluating WE for performance improvement.

Delivery of Instructions via Mobile Social Media App Increases Quality of Bowel Preparation.

BACKGROUND & AIMS: Bowel preparation is closely linked to the quality of colonoscopy. We investigated whether delivery of instructions via a social media app increases the quality of colonoscopy by improving adequacy of bowel preparation. METHODS: We performed a prospective study at 3 endoscopic centers in China of 770 colonoscopy outpatients (18-80 years old) with convenient access to Wechat (a widely used mobile social media app) from May through November 2014. Patients were randomly assigned to groups that received standard education along with delivery of interactive information via Wechat (n = 387) or standard education (controls, n = 383). The primary outcome was proportion of patients with adequate bowel preparation (Ottawa score <6). Secondary outcomes included rates of adenoma detection and cecal intubation, cecal intubation time, rates of incomplete compliance with instructions, and patient willingness to repeat bowel preparation. RESULTS: Demographic features were comparable between the groups. A higher proportion of patients in the group that received social media instruction had adequate bowel preparation than the control group (82.2% vs 69.5%, P < .001). Among patients with successful colonoscopies, the group that received social media instruction had lower mean total and segmental Ottawa scores (P < .05). A higher proportion of patients receiving social media instruction also had cecal intubation (97.2% vs 93.2% in controls, P = .014) and were found to have adenomas (18.6% vs 12.0% in controls, P = .012). CONCLUSIONS: Instruction via a mobile social media app, in conjunction with regular instruction, increases subjective measures of adequacy of bowel preparation. Use of the app significantly increased the proportion of patients with successful cecal intubation and in whom adenomas were detected, indicating increased quality of colonoscopy. ClinicalTrials.gov number: NCT02140827.