Improved outcome models with denoising diffusion.

PURPOSE: Radiotherapy outcome modelling often suffers from class imbalance in the modelled endpoints. One of the main options to address this issue is by introducing new synthetically generated datapoints, using generative models, such as Denoising Diffusion Probabilistic Models (DDPM). In this study, we implemented DDPM to improve performance of a tumor local control model, trained on imbalanced dataset, and compare this approach with other common techniques. METHODS: A dataset of 535 NSCLC patients treated with SBRT (50 Gy/5 fractions) was used to train a deep learning outcome model for tumor local control prediction. The dataset included complete treatment planning data (planning CT images, 3D planning dose distribution and patient demographics) with sparsely distributed endpoints (6-7 % experiencing local failure). Consequently, we trained a novel conditional 3D DDPM model to generate synthetic treatment planning data. Synthetically generated treatment planning datapoints were used to supplement the real training dataset and the improvement in the model's performance was studied. Obtained results were also compared to other common techniques for class imbalanced training, such as Oversampling, Undersampling, Augmentation, Class Weights, SMOTE and ADASYN. RESULTS: Synthetic DDPM-generated data were visually trustworthy, with Fréchet inception distance (FID) below 50. Extending the training dataset with the synthetic data improved the model's performance by more than 10%, while other techniques exhibited only about 4% improvement. CONCLUSIONS: DDPM introduces a novel approach to class-imbalanced outcome modelling problems. The model generates realistic synthetic radiotherapy planning data, with a strong potential to increase performance and robustness of outcome models.

High-resolution MRI synthesis using a data-driven framework with denoising diffusion probabilistic modeling.

Objective. High-resolution magnetic resonance imaging (MRI) can enhance lesion diagnosis, prognosis, and delineation. However, gradient power and hardware limitations prohibit recording thin slices or sub-1 mm resolution. Furthermore, long scan time is not clinically acceptable. Conventional high-resolution images generated using statistical or analytical methods include the limitation of capturing complex, high-dimensional image data with intricate patterns and structures. This study aims to harness cutting-edge diffusion probabilistic deep learning techniques to create a framework for generating high-resolution MRI from low-resolution counterparts, improving the uncertainty of denoising diffusion probabilistic models (DDPM).Approach. DDPM includes two processes. The forward process employs a Markov chain to systematically introduce Gaussian noise to low-resolution MRI images. In the reverse process, a U-Net model is trained to denoise the forward process images and produce high-resolution images conditioned on the features of their low-resolution counterparts. The proposed framework was demonstrated using T2-weighted MRI images from institutional prostate patients and brain patients collected in the Brain Tumor Segmentation Challenge 2020 (BraTS2020).Main results. For the prostate dataset, the bicubic interpolation model (Bicubic), conditional generative-adversarial network (CGAN), and our proposed DDPM framework improved the noise quality measure from low-resolution images by 4.4%, 5.7%, and 12.8%, respectively. Our method enhanced the signal-to-noise ratios by 11.7%, surpassing Bicubic (9.8%) and CGAN (8.1%). In the BraTS2020 dataset, the proposed framework and Bicubic enhanced peak signal-to-noise ratio from resolution-degraded images by 9.1% and 5.8%. The multi-scale structural similarity indexes were 0.970 ± 0.019, 0.968 ± 0.022, and 0.967 ± 0.023 for the proposed method, CGAN, and Bicubic, respectively.Significance. This study explores a deep learning-based diffusion probabilistic framework for improving MR image resolution. Such a framework can be used to improve clinical workflow by obtaining high-resolution images without penalty of the long scan time. Future investigation will likely focus on prospectively testing the efficacy of this framework with different clinical indications.

CBCT-Based synthetic CT image generation using conditional denoising diffusion probabilistic model.

BACKGROUND: Daily or weekly cone-beam computed tomography (CBCT) scans are commonly used for accurate patient positioning during the image-guided radiotherapy (IGRT) process, making it an ideal option for adaptive radiotherapy (ART) replanning. However, the presence of severe artifacts and inaccurate Hounsfield unit (HU) values prevent its use for quantitative applications such as organ segmentation and dose calculation. To enable the clinical practice of online ART, it is crucial to obtain CBCT scans with a quality comparable to that of a CT scan. PURPOSE: This work aims to develop a conditional diffusion model to perform image translation from the CBCT to the CT distribution for the image quality improvement of CBCT. METHODS: The proposed method is a conditional denoising diffusion probabilistic model (DDPM) that utilizes a time-embedded U-net architecture with residual and attention blocks to gradually transform the white Gaussian noise sample to the target CT distribution conditioned on the CBCT. The model was trained on deformed planning CT (dpCT) and CBCT image pairs, and its feasibility was verified in brain patient study and head-and-neck (H&N) patient study. The performance of the proposed algorithm was evaluated using mean absolute error (MAE), peak signal-to-noise ratio (PSNR) and normalized cross-correlation (NCC) metrics on generated synthetic CT (sCT) samples. The proposed method was also compared to four other diffusion model-based sCT generation methods. RESULTS: In the brain patient study, the MAE, PSNR, and NCC of the generated sCT were 25.99 HU, 30.49 dB, and 0.99, respectively, compared to 40.63 HU, 27.87 dB, and 0.98 of the CBCT images. In the H&N patient study, the metrics were 32.56 HU, 27.65 dB, 0.98 and 38.99 HU, 27.00, 0.98 for sCT and CBCT, respectively. Compared to the other four diffusion models and one Cycle generative adversarial network (Cycle GAN), the proposed method showed superior results in both visual quality and quantitative analysis. CONCLUSIONS: The proposed conditional DDPM method can generate sCT from CBCT with accurate HU numbers and reduced artifacts, enabling accurate CBCT-based organ segmentation and dose calculation for online ART.

Few-shot biomedical image segmentation using diffusion models: Beyond image generation.

BACKGROUND: Medical image analysis pipelines often involve segmentation, which requires a large amount of annotated training data, which is time-consuming and costly. To address this issue, we proposed leveraging generative models to achieve few-shot image segmentation. METHODS: We trained a denoising diffusion probabilistic model (DDPM) on 480,407 pelvis radiographs to generate 256 âœ• 256 px synthetic images. The DDPM was conditioned on demographic and radiologic characteristics and was rigorously validated by domain experts and objective image quality metrics (Frechet inception distance [FID] and inception score [IS]). For the next step, three landmarks (greater trochanter [GT], lesser trochanter [LT], and obturator foramen [OF]) were annotated on 45 real-patient radiographs; 25 for training and 20 for testing. To extract features, each image was passed through the pre-trained DDPM at three timesteps and for each pass, features from specific blocks were extracted. The features were concatenated with the real image to form an image with 4225 channels. The feature-set was broken into random patches, which were fed to a U-Net. Dice Similarity Coefficient (DSC) was used to compare the performance with a vanilla U-Net trained on radiographs. RESULTS: Expert accuracy was 57.5 % in determining real versus generated images, while the model reached an FID = 7.2 and IS = 210. The segmentation UNet trained on the 20 feature-sets achieved a DSC of 0.90, 0.84, and 0.61 for OF, GT, and LT segmentation, respectively, which was at least 0.30 points higher than the naively trained model. CONCLUSION: We demonstrated the applicability of DDPMs as feature extractors, facilitating medical image segmentation with few annotated samples.

Improving Bowel Management in Children With Spina Bifida.

OBJECTIVES: In individuals with spina bifida (SB), bowel incontinence is associated with lower quality of life and lower likelihood of employment. In an effort to maximize bowel continence in children and adolescents, we created a bowel management assessment and follow-up protocol in a multidisciplinary clinic. Here we report the results of this protocol using quality-improvement methodology. METHODS: Continence was defined as no unplanned bowel movements. Our protocol involved: (1) a standardized 4-item questionnaire about bowel continence and consistency; (2) if the patient was not achieving continence, an intervention starting with oral medication (stimulant and/or osmotic laxatives), and/or suppositories (glycerin or bisacodyl) followed by an escalation to trans-anal irrigation, or continence surgery; and (3) follow-up phone calls at regular intervals to monitor progress and make changes as needed. Results are summarized with descriptive statistics. RESULTS: We screened 178 eligible patients in the SB clinic. Eighty-eight agreed to participate in the bowel management program. Of those who did not participate, the majority (68/90, 76%) were already achieving continence with their bowel regimen. Of children in the program, most (68/88, 77%) had a diagnosis of meningomyelocoele. At 1 year, the proportion of patients who were bowel accident free improved to 46% (vs 22% initially, P = 0.0007). CONCLUSIONS: A standardized bowel management protocol, primarily the use of suppositories and trans-anal irrigation to achieve social continence, as well as frequent telephone follow-up, can reduce bowel incontinence in children and adolescents with SB.

Efficacy of different bowel preparation regimen volumes for colorectal cancer screening and compliance with European Society of Gastrointestinal Endoscopy performance measures.

BACKGROUND: Various volumes of bowel preparation are used in clinical practice. There is conflicting data on the effectiveness of individual regimens. This study aims to evaluate the efficacy and compliance of currently used bowel preparations with the European Society of Gastrointestinal Endoscopy (ESGE) performance measures using data of the Dutch nationwide colorectal cancer screening (CRC) program. METHODS: In a prospective, multicenter endoscopy database, we identified all CRC screening colonoscopies performed in 15 Dutch endoscopy centers from 2016 to 2020. We excluded procedures without documented bowel preparation or the Boston Bowel Preparation Scale (BBPS) score. Bowel preparation regimens were categorized into three groups, that is, 4-L (polyethylene glycol (PEG)), 2-L (2-L PEG with ascorbic acid) and ≤1-L volumes (sodium picosulfate with magnesium citrate, 1L-PEG with sodium sulfate and ascorbic acid or oral sulfate solution). European Society of Gastrointestinal Endoscopy performance measures included adequate BBPS score (≥6) (>90%), cecal intubation rate (CIR, >90%), adenoma detection rate (ADR, >25%) and polyp detection rate (PDR, >40%). Logistic regression was performed to identify predictive factors for adequate BBPS and patient discomfort. RESULTS: A total of 39,042 CRC screening colonoscopies were included. Boston Bowel Preparation Scale scores, CIR, ADR and PDR for 4L, 2L and ≤1L regimens all met the minimum ESGE performance measures standards. However, an adequate BBPS score was more frequently seen with 2L regimens (98.0%) as compared to 4L (97.1%) and ≤1L regimens (97.0%) (p < 0.001), respectively. In addition, CIR was higher for ≤1L (98.4%) versus 4L (97.7%) and 2L (97.9%) regimens (p = 0.001), ADR higher for lower volume (≤1L (60.0%) and 2L (61.2)) versus higher volume (4L (58.6%)) regimens (p < 0.001), and PDR higher for ≤1L (70.0%) and 2L (70.8%) versus 4L (67.2%) regimens (p < 0.001). Boston Bowel Preparation Scale for ≤1L regimens was higher when combined with bisacodyl (97.3%) than without (95.6%) (p < 0.001). Overall, bisacodyl use was independently associated with higher patient discomfort (odds ratios = 1.47, confidence intervals = 1.26-1.72). CONCLUSIONS: Despite variations in bowel preparation volumes, all regimens meet the minimum ESGE performance measures for bowel preparation and other quality parameters. Boston Bowel Preparation Scale can be further improved if ultra low volume regimens are combined with bisacodyl. The choice for either bowel preparation volume can therefore be based on volume-tolerance and patient preference.

Sleep Disturbances, Bowel Movement Kinetics, and Travel Interruption With Bowel Preparation: A Bowel CLEANsing National Initiative Substudy.

INTRODUCTION: We investigated sleep disturbances, bowel movement (BM) kinetics, and travel experience with different bowel preparation regimens in a substudy of patients enrolled in a randomized multicenter Canadian clinical trial. METHODS: Patients scheduled to have a colonoscopy between 7:30 am and 10:30 am (early morning) were randomized to (i) 4-L single-dose polyethylene glycol (PEG) given in the evening before, (ii) 2-L split-dose PEG (+bisacodyl 15 mg), or (iii) 4-L split-dose PEG. Patients scheduled to undergo a colonoscopy between 10:30 am and 4:30 pm (afternoon) were randomized to (iv) 2-L single-dose PEG (+bisacodyl 15 mg) in the morning, (v) 2-L split-dose PEG (+bisacodyl 15 mg), or (vi) 4-L split-dose PEG. Patients were asked to record information on BM kinetics, sleep, and travel to the endoscopy unit. Continuous and categorical variables were compared between groups using a Kruskal-Wallis test or χ 2 test, respectively. Intention-to-treat analyses were performed. RESULTS: Overall, 641 patients were included in this substudy. Patients undergoing early morning colonoscopies reported the most awakenings in the night when assigned to 4-L single-dose day-before PEG and the highest reduction in sleep hours when assigned to 4-L split-dose PEG. There were no significant between-group differences in urgent BMs, fecal incontinence episodes, or travel interruptions. Overall, 17% of those traveling for more than an hour had to stop for a BM during travel, with no significant difference between groups. DISCUSSION: Day-before and split-dose high-volume PEG regimens for colonoscopies scheduled before 10:30 am lead to the greatest sleep disturbance.

Risk factors for inadequate bowel preparation in patients using high- and low-volume cleansing products.

INTRODUCTION: Bowel preparation is crucial for colonoscopy completeness and lesions detection. Today, several cleansing products are equally recommended by guidelines, irrespective of patients' characteristics. Identification of preparation-specific risk factors for inadequate bowel preparation may lead to a personalized prescription of cleansing products to refine patients' tolerance and improve endoscopic outcomes. METHODS: We prospectively enrolled consecutive outpatients referred for colonoscopy using either a high-volume [HV: 4 l polyethylene glycol (PEG)] or a low-volume (LV: 2 l PEG + bisacodyl) preparation. Day-before regimen or split-dose regimen was used for morning or afternoon colonoscopies, respectively. Univariate and multivariate analyses were conducted to identify risk factors related to inadequate bowel preparation, according to the Boston bowel preparation scale for HV and LV preparations. RESULTS: We enrolled 2040 patients, of which 1815 were included in the final analysis (average age 60.6 years, 50.2% men). Half of them (52%) used LV preparation. Adequate preparation was achieved by 87.6% without differences between the HV and LV groups (89.2% vs. 86.6%; P = 0.098). The use of day-before regimen and incomplete assumption of PEG were independent predictors of poor visibility for either HV or LV preparation. However, different specific risk factors for HV [diabetes: odds ratio (OR), 3.81; 95% confidence interval (CI), 1.91-7.58; low level of instruction: OR, 1.95; 95% CI, 1.11-3.44; and previous abdominal surgery: OR, 2.27; 95% CI, 1.20-4.30] and for LV (heart disease: OR, 2.06; 95% CI, 1.09-3.88; age > 65 years: OR, 1.51; 95% CI, 1.01-2.27) preparations were identified. CONCLUSION: Day-before preparation and incomplete assumption of the purgative agents affect bowel visibility irrespective of the preparation volume. LV should be preferred to HV preparations in patients with diabetes, low level of instruction, and previous abdominal surgery, whereas an HV preparation should be preferred in patients with heart disease and in older patients.

Effect of Bacillus coagulans SNZ 1969 on the Improvement of Bowel Movement in Loperamide-Treated SD Rats.

Bacillus coagulans SNZ 1969 (B. coagulans SNZ 1969) is a spore-forming bacterium reported to be effective in attenuating constipation. However, there is no study on whether B. coagulans SNZ 1969 could improve constipation through mucin secretion and changes in intestinal hormones. To address this knowledge gap, rats were orally administrated with various treatments for four weeks. The normal control (NOR) group received saline only. There were four constipation-induced groups. The LOP group received only loperamide (LOP), a constipation-inducing agent. The BIS group received both LOP and Bisacodyl (BIS, a constipation treatment agent). The SNZ-L group received both LOP and B. coagulans SNZ 1969 at 1 × 108 CFU/day. The SNZ-H group received LOP and B.coagulans SNZ 1969 at 1 × 1010 CFU/day. As indicators of constipation improvement, fecal pellet weight, fecal water content, gastrointestinal transit time, and intestinal motility were measured. Mucus secretion in the colon was determined by histological colon analysis and mucin-related gene expressions. Gastrointestinal (GI) hormones were also measured. SNZ-L and SNZ-H groups showed significantly increased fecal weights, fecal water contents, and intestinal motility than the LOP group. SNZ-L and SNZ-H groups also showed higher secretion of mucin in the colon and mRNA expression levels of Mucin 2 and Aquaporin 8 than the LOP group. The SNZ-H group showed significantly increased substance P but significantly decreased somatostatin and vasoactive intestinal peptide than the LOP group. The results of this study suggest that B. coagulans SNZ 1969 intake could attenuate constipation through mucin secretion and alteration of GI hormones.

Exploring the pathophysiology of LARS after low anterior resection for rectal cancer with high-resolution colon manometry.

BACKGROUND: A total mesorectal excision for rectal cancer-although nerve- and sphincter-sparing-can give rise to significant bowel symptoms, commonly referred to as low anterior resection syndrome (LARS). The exact pathophysiology of this syndrome still remains largely unknown, and the impact of radical surgery on colonic motility has only been scarcely investigated. METHODS: High-resolution colon manometry was performed in patients, 12-24 months after restoration of transit. Patients were divided into two groups: patients with major LARS and no/minor LARS, according to the LARS-score. Colonic motor patterns were compared, and the relationship of these patterns with the LARS-scores was investigated. KEY RESULTS: Data were analyzed in 18 patients (9 no/minor LARS, 9 major LARS). Cyclic short antegrade motor patterns did occur more in patients with major LARS (total: p = 0.022; post-bisacodyl: p = 0.004) and were strongly correlated to LARS-scores after administering bisacodyl (p < 0.001). High amplitude propagating contractions (HAPC's) that started in the proximal colon and ended in the mid-section of the colon occurred significantly less in patients with major LARS compared with patients with no/minor LARS (p = 0.015). CONCLUSIONS AND INFERENCES: The occurrence of more cyclic short antegrade motor patterns and less HAPC's (from the proximal to the mid-colon) is more prevalent in patients with major LARS. These findings help to understand the differences in pathophysiology in patients developing major versus no/minor bowel complaints after TME for rectal cancer.

An Israeli national survey on ischemic colitis induced by pre-colonoscopy bowel preparation (R1).

Background and study aims: Ischemic colitis (IC) may occur as a complication of colonoscopy. The aim of this study was to characterize patients with IC that occurred after exposure to bowel preparation laxatives, prior to an elective colonoscopy. Patients and methods: A survey among Israeli gastroenterologists. Information was collected regarding individual cases. Results: Eight patients, who developed IC after bisacodyl ingestion that was taken as part of pre-colonoscopy bowel preparation protocol, were reported. In all patients, severe abdominal pain and/or hematochezia started shortly after the ingestion of the first dose of bisacodyl. IC was found in 7 patients during the planned colonoscopy and in 1 patient using computerized tomography. All patients received supportive treatment and recovered. Conclusions: IC induced by bisacodyl is a rare phenomenon. Regardless of being rare, we would advise withholding bisacodyl bowel preparation in elderly subjects with risk factors for IC that are scheduled for a colonoscopy.

Predictive factors for inadequate bowel cleansing in colon capsule endoscopy.

BACKGROUND AND AIMS: Achieving adequate bowel cleansing is of utmost importance for the efficiency of colon capsule endoscopy (CCE). However, information about predictive factors is lacking. The aim of this study was to assess the predictive factors of poor bowel cleansing in the CCE setting. METHODS: In this observational study, 126 patients who underwent CCE at two tertiary care hospitals were included between June 2017 and January 2020. Participants prepared for bowel cleansing with a 1-day clear liquid diet, a 4-L split-dose polyethylene glycol regimen and boosters with sodium phosphate, sodium amidotrizoate and meglumine amidotrizoate. Domperidone tablets and bisacodyl suppositories were administered when needed. Overall and per-segment bowel cleansing was evaluated using a CCE cleansing score. Simple and multiple logistic regression analysis were carried out to assess poor bowel cleansing and excretion rate predictors. RESULTS: Overall bowel cleansing was optimal in 53 patients (50.5%). Optimal per-segment bowel cleansing was achieved as follows: cecum (86 patients; 74.8%), transverse colon (91 patients; 81.3%), distal colon (81 patients; 75%) and rectum (64 patients; 66.7%). In the univariate analysis, elderly (OR, 1.03; 95% CI (1.01-1.076)) and constipation (OR, 3.82; 95% CI (1.50-9.71)) were associated with poor bowel cleansing. In the logistic regression analysis, constipation (OR, 3.77; 95% CI (1.43-10.0)) was associated with poor bowel cleansing. No variables were significantly associated with the CCE device excretion rate. CONCLUSION: Our results suggest that constipation is the most powerful predictor of poor bowel cleansing in the CCE setting. Tailored cleansing protocols should be recommended for these patients.

The Bowel CLEANsing National Initiative: High-Volume Split-Dose Vs Low-Volume Split-Dose Polyethylene Glycol Preparations: A Randomized Controlled Trial.

BACKGROUND & AIMS: The aim of this study was to compare high-volume polyethylene glycol (PEG) with low-volume PEG with bisacodyl split-dosing regimens. METHODS: Adult outpatients in 10 Canadian tertiary hospitals were randomized, stratified by morning or afternoon colonoscopy, to high-volume split-dose PEG (2 L + 2 L) (High-SD) or low volume (1 L + 1 L) + bisacodyl (15 mg) PEG (Low-SD), with a second randomization to liquid or low-residue diets. The primary end point, using noninferiority hypothesis testing, was adequate bowel cleansing (Boston Bowel Preparation Scale total score of ≥6, with each of 3 colonic segments subscores ≥2). Secondary objectives were willingness to repeat the preparation, withdrawal time, cecal intubation, and polyp detection rates. RESULTS: Over 29 months, 2314 subjects were randomized to High-SD (N = 1157) or Low-SD (N = 1157) (mean age, 56.2 ± 13.4 y; 52.1% women). Colonoscopy indications were 38.2% diagnostic, 36.8% screening, and 25.0% surveillance, with no between-group imbalances in patient characteristics. Low-SD satisfied noninferiority criteria vs High-SD for adequate bowel cleanliness with only marginally inferior results (90.1% vs 88.1%; P = .02; difference, 2.0%; 95% CI [0.0%; 4.5%]). High-SD was associated with lower willingness to repeat (66.9% vs 91.9%; P < .01), was less well tolerated (7.3 ± 2.3 vs 8.1 ± 1.9; P < .01), causing more symptoms. No differences in procedural outcomes were noted except for more frequent cecal intubation rates after High-SD (97.4% vs 95.6%; P = .02). Among the High-SD group, adequate bowel preparation was greater after a clear liquid diet (93.6% vs 87.9%; P < .01), a finding not seen in the Low-SD group. CONCLUSIONS: Low-SD is noninferior to High-SD in providing adequate bowel preparation. Low-SD results in fewer symptoms, with greater willingness to repeat and tolerability. The overall impact of diet was modest.The study was approved by the research ethic boards from all sites and was registered at ClinicalTrials.gov (NCT02547571).

A Multicenter Randomized Controlled Trial Comparing Two Bowel Cleansing Regimens for Colonoscopy After Failed Bowel Preparation.

BACKGROUND & AIMS: Failed bowel preparation for colonoscopy occurs commonly, but the optimal regimen for the subsequent attempt is unknown. High-volume preparations often are used but are not well studied. The objective of this study was to compare the efficacy, tolerability, and safety of 2 regimens for use after failed bowel preparation. METHODS: A multicenter, endoscopist-blinded randomized controlled trial was conducted in patients who previously failed bowel preparation despite adequate compliance. Patients were randomized to 1 of 2 split polyethylene glycol (PEG) regimens, preceded by 15 mg bisacodyl: PEG 2 L the evening before and 2 L the day of colonoscopy (PEG 2+2L+bisacodyl), or 4 L and 2 L (PEG 4+2L+bisacodyl). All patients followed a low-fiber diet on both the third and second day before the procedure, followed by a clear fluid diet the day before and the morning of the colonoscopy. The primary outcome was adequate bowel preparation, defined as a Boston Bowel Preparation Scale total score of 6 or higher, with all segment scores of 2 or higher. Secondary outcomes included adenoma detection rate, advanced adenoma detection rate, sessile serrated lesion detection, cecal intubation rate, tolerability, and adverse events. RESULTS: A total of 196 subjects were randomized at 4 academic centers in Canada (mean age, 60.7 y; SD, 11.4 y; 44.9% were women). There were no significant differences between the PEG 2+2L+bisacodyl and the PEG 4+2L+bisacodyl groups in achieving adequate bowel preparation (91.2% vs 87.6%; P = .44). There were no significant differences with regard to mean adenoma detection rate (37.4% vs 31.5%; P = .41), advanced adenoma detection rate (18.7% vs 11.2%; P = .16), sessile serrated lesion detection (8.8% vs 5.6%; P = .41), and cecal intubation rate (96.7% vs 92.1%; P = .19). The 2 regimens were similarly well tolerated, but PEG 2+2L+bisacodyl was associated with a higher willingness to repeat the bowel preparation (91.2% vs 66.2%; P < .001). CONCLUSIONS: Split-dose 4 L-PEG with 15 mg bisacodyl, along with dietary restrictions, has similar efficacy as a higher-volume preparation, and should be considered for patients who previously failed bowel preparation (ClinicalTrials.gov number, NCT02976805).

Bisacodyl Suppresses TGF-α-Induced MUC5AC Production in NCI-H292 Cells.

MUC5AC overproduction is commonly observed in chronic inflammatory lung diseases and worsens these conditions. Therefore, drugs that inhibit MUC5AC production are urgently needed. To identify novel drugs directly inhibiting MUC5AC production, 640 already approved drugs were screened. We found that the laxative bisacodyl suppressed transforming growth factor (TGF)-α-induced MUC5AC production in a concentration-dependent manner. Additionally, bisacodyl also suppressed TGF-α-induced MUC5AC mRNA expression in the same concentration range. These results suggested that bisacodyl could be a new drug for treating mucin overproduction.

Heat-inactivated Lactobacillus plantarum nF1 promotes intestinal health in Loperamide-induced constipation rats.

Constipation is a common condition that affects individuals of all ages, and prolonged constipation needs to be prevented to avoid potential complications and reduce the additional stress on individuals with pre-medical conditions. This study aimed to evaluate the effects of heat-inactivated Lactobacillus plantarum (HLp-nF1) on loperamide-induced constipation in rats. Constipation-induced male rats were treated orally with low to high doses of HLp-nF1 and an anti-constipation medication Dulcolax for five weeks. Study has 8 groups, control group; loperamide-treated group; Dulcolax-treated group; treatment with 3.2 × 1010, 8 × 1010 and 1.6 × 1011, cells/mL HLp-nF1; Loperamide + Dulcolax treated group. HLp-nF1 treated rats showed improvements in fecal pellet number, weight, water content, intestinal transit length, and contractility compared to the constipation-induced rats. Also, an increase in the intestine mucosal layer thickness and the number of mucin-producing crypt epithelial cells were observed in HLp-nF1-treated groups. Further, the levels of inflammatory cytokines levels were significantly downregulated by treatment with HLp-nF1 and Dulcolax. Notably, the metagenomics sequencing analysis demonstrated a similar genus pattern to the pre-preparation group and control with HLp-nF1 treatment. In conclusion, the administration of >3.2 × 1010 cells/mL HLp-nF1 has a positive impact on the constipated rats overall health.

Noninferiority clinical trial comparing the bowel cleansing efficacy of sodium phosphate tablets (Quiklean®) with a polyethylene glycol/bisacodyl kit.

BACKGROUND: Efficient bowel cleansing is essential for a successful colonoscopy, but the ideal cleansing agent, volume, and pharmaceutical dosage form have yet to be determined. Small-volume cleansers enhance patient compliance. AIM: To compare the bowel cleansing efficacy of 32-tablet sodium phosphate (Quiklean®) with 2-L polyethylene glycol (PEG)/bisacodyl (Klean-Prep/ Dulcolax®) under identical dietary recommendations. METHODS: This multicenter, randomized, parallel-group, noninferiority clinical trial enrolled 472 outpatients, randomized 456 subjects, and scheduled 442 subjects to undergo colonoscopy (Quiklean® = 222 and Klean-Prep/Dulcolax® = 220). After bowel preparation, a colonoscopist performed the colonoscopy with video recorded for rating. The primary efficacy endpoint was the bowel cleansing quality using the Aronchick Scale. The secondary endpoints were the bowel cleansing efficacy of three colon segments, tolerability and acceptability, safety using the Ottawa bowel preparation scale, questionnaires by subjects, and monitoring of adverse events. RESULTS: Success rates (Excellent + Good) of the bowel cleansing quality by Aronchick Scale were 98.6% (n = 205) and 97.6% (n = 204) in the Quiklean® and Klean-Prep/Dulcolax® groups, respectively. Quiklean® demonstrated noninferiority over Klean-Prep/Dulcolax® in colon cleansing efficacy. Quicken showed better tolerability and acceptability in the overall experience (was rated as excellent; 24.0% vs 17.2%; P = 0.0016) and the taste of the study preparation (was rated as excellent, 23.1% vs 13.4%; P < 0.0001) than Klean-Prep/Dulcolax®. Safety profiles did not differ between the two groups. Our data indicate that Quiklean® is an adequate, well-tolerated bowel cleansing preparation compared with the standard comparator Klean-Prep/Dulcolax®. CONCLUSION: Quiklean® is sodium phosphate tablets available on Taiwan's market for bowel preparation; it potentially offers patients an alternative to standard large-volume bowel preparation regimens and may, therefore, increase positive attitudes toward colonoscopies and participation rates.

Split-Dose Regimen With Bisacodyl Increases the Quality of Bowel Preparation for Colonoscopy.

The aim of the present study was to compare 2 different bowel preparations procedures (split-dose with PicoPrep and bisacodyl vs. same-day preparation with PicoPrep) in patients undergoing colonoscopy with regard to quality of bowel preparation, compliance, and willingness to repeat. A retrospective quasi-experimental investigation was conducted. Adults with outpatient diagnostic and surveillance colonoscopies were included. A total of 540 patients participated: group 'split-dose with bisacodyl' (n = 293) and group 'same-day' (n = 247). Patients in group 'split-dose with bisacodyl' had a higher chance for having an excellent quality of bowel preparation (21.2%; 95% CI [13.5, 28.9]) and a reduced risk of an incomplete colonoscopy (4.1%; 95% CI [1.2, 7.0]). Group 'split-dose with bisacodyl' drank more fluid, had more nightly visits to the bathroom, and had more bathroom stops on the way to the endoscopic site. No differences were found between groups regarding adenoma detection rate, withdrawal time, overall time of colonoscopy, well-being during cleansing, patient satisfaction, the professional's assessment of the patient's tolerability of colonoscopy, and willingness to repeat the bowel preparation process. The split-dose regimen with PicoPrep and bisacodyl is now the standard bowel preparation procedure for patients undergoing elective colonoscopy as it is superior to the same-day regimen with PicoPrep regarding colon cleansing and incomplete colonoscopy. Hence, the written and verbal information at our institution regarding the bowel preparation procedure was altered according to the split-dose regimen, emphasizing the importance of adequate oral fluid intake and complete intake of the solution in order to ensure a safe and effective procedure.