A randomized prospective study comparing the effect of low-volume bowel preparations for colonoscopy preparation in China.

AIM: To evaluate the effect of sodium picosulfate/magnesium citrate (SPMC) and 3 L split-dose polyethylene glycol (PEG) with or without dimethicone on bowel preparation before colonoscopy. METHODS: In this multicenter, prospective, randomized, controlled study conducted from April 2021 to December 2021, consecutive adult patients scheduled for colonoscopy were prospectively randomized into four groups: SPMC, SPMC plus dimethicone, 3 L PEG, and 3 L PEG plus dimethicone. Primary endpoint was colon cleansing based on Boston Bowel Preparation Scale (BBPS). Secondary endpoints were bubble score, time to cecal intubation, adenoma detection rate (ADR), patient safety and compliance, and adverse events. RESULTS: We enrolled 223 and 291 patients in SPMC and 3 L PEG group, respectively. The proportion with acceptable bowel cleansing, total BBPS score and cecal intubation time were similar in all four subgroups (p > 0.05). Patient-reported acceptability and tolerability was significantly greater in SPMC than 3 L PEG group (p < 0.001); adverse events were significantly lower in SPMC than latter group (p < 0.001). ADR in both groups was greater than 30%. CONCLUSION: SPMC had significantly higher acceptability and tolerability than 3 L PEG, however, was similar in terms of bowel-cleansing effect and cecal intubation time and hence can be used before colonoscopy preparation.

[The role of mitochondrial dysfunction in the stabilization of the glaucomatous process]. / Znachenie mitokhondrial'noi disfunktsii v stabilizatsii glaukomnogo protsessa.

Many key aspects of retinal ganglion cell (RGC) neurodegeneration in glaucoma are associated with mitochondrial dysfunction. Understanding the mechanisms and relationships between structural and functional changes in mitochondria would be beneficial for developing mitochondria-targeted therapeutic strategies to protect RGCs from glaucomatous neurodegeneration. PURPOSE: This study determines the extent of mitochondrial dysfunction in patients with primary open-angle glaucoma (POAG) and evaluates the potential for stabilizing the glaucomatous process by improving mitochondrial functional activity and energy production by therapy with Mexidol and Mexidol FORTE 250. MATERIAL AND METHODS: The study included 80 patients with moderate POAG with compensated intraocular pressure and 20 healthy volunteers. The extent of mitochondrial dysfunction was assessed by measuring the activity levels of mitochondrial enzymes: succinate dehydrogenase (SDH) and α-glycerophosphate dehydrogenase (α-GPDH) in peripheral blood lymphocytes using cytochemical analysis and cytometric morphology and density analysis (cytomorphodensitometry). Patients in the main group received sequential therapy with Mexidol as follows: Mexidol solution for intravenous and intramuscular administration at 50 mg/ml, 300 mg daily intramuscularly for 14 days, followed by Mexidol FORTE 250 tablets, one tablet three times daily for 56 days. Stabilization of glaucomatous optic neuropathy during treatment was evaluated using a comprehensive set of perimetric, electrophysiological, and structural-topographical methods at 14, 56, and 90 days. RESULTS: Sequential therapy in the main group resulted in a significant increase in mitochondrial enzyme activity at 14 and 56 days compared to baseline, with a gradual regression by the end of the observation period (90 days). This was accompanied by an increase in the number of mitochondria and an increase in their optical density as measured by cytomorphodensitometry. The improvement in mitochondrial enzyme activity at 14 and 56 days was associated with positive changes in the structural and functional parameters of the retina, as evidenced by static perimetry, optical coherence tomography, and a series of electrophysiological tests. CONCLUSION: The obtained data can be used to optimize POAG therapy by reducing mitochondrial dysfunction and stabilizing glaucomatous optic neuropathy.

Effect of Xymedon and Mexidol in Combination with Antineoplastic Drugs on Spermatogenesis Indicators and Functional State of Spermatozoa in Rats with Walker-256 Carcinoma.

We compared the effect of Xymedon (100 mg/kg), Mexidol (50 mg/kg), and their combination on spermatogenesis indicators and functional state of spermatozoa in rats with Walker-256 carcinoma treated with doxorubicin (4 mg/kg) and cyclophosphamide (45 mg/kg) (once intraperitoneally on day 11 after tumor cells transplantation). Xymedon and Mexidol were injected intramuscularly for 10 days starting from day 11 of the experiment. The studied parameters were evaluated on experimental days 14 and 21. We have established that gonadoprotective effect of Xymedon developed gradually and persisted longer than that of Mexidol. It manifested in an increase in the number of epithelial spermatogenesis cells (spermatogonia by 3.2 times, early spermatids by 2.2 times, late spermatids by 2.9 times, and Leydig cells by 4 times) in the testes and also the proportion of viable progressively and non-progressively motile epididymal spermatozoa (by 2 times). The combination of Xymedon and Mexidol stimulated spermatogenesis (with restoration of the initial level of spermatocytes, an increase in the number of early spermatids by 65.5 and 99% in comparison with Xymedon alone and Mexidol alone, respectively) and increased the number of viable epididymal spermatozoa more effectively than Xymedon and Mexidol alone by 54 and 60%, respectively.

The impact of low- versus standard-volume bowel preparation on participation in primary screening colonoscopy: a randomized health services study.

BACKGROUND: The aim of this study was to evaluate the impact of low-volume vs. standard-volume bowel preparation on participation in screening colonoscopy, bowel preparation quality, and lesion detection rates. METHODS: This was a multicenter, randomized, health services study within the population-based primary colonoscopy screening program in Poland. Individuals aged 55 - 62 years were randomized in a 1:1 ratio to bowel preparation with a low-volume (0.3 L sodium picosulfate with magnesium citrate) or standard-volume (4 L polyethylene glycol) regimen and then invited to participate in screening colonoscopy. The primary outcome measure was the rate of participation in screening colonoscopy. Compliance with the assigned bowel preparation, bowel preparation quality, and lesion detection rates were also evaluated. RESULTS: A total of 13 621 individuals were randomized and 13 497 were analyzed (6752 in the low-volume group and 6745 in the standard-volume group). The participation rate (16.6 % vs. 15.5 %; P = 0.08) and compliance rate (93.3 % vs. 94.1 %; P = 0.39) did not differ significantly between the groups. In the low-volume group, fewer participants had adequate bowel preparation compared with the standard-volume group (whole colon 79.0 % vs. 86.4 %, P < 0.001; proximal colon 80.1 % vs. 87.3 %, P < 0.001). Detection rates of advanced adenoma (AADR) and advanced serrated polyps (ASPDR) were lower in the low-volume group than in the standard-volume group (AADR in the proximal colon 2.6 % vs. 4.3 %, P = 0.02; ASPDR in the whole colon 2.0 % vs. 3.3 %, P = 0.04; ASPDR in the proximal colon 1.0 % vs. 1.9 %, P = 0.048). CONCLUSION: When compared with a standard-volume bowel preparation with polyethylene glycol, low-volume bowel preparation with sodium picosulfate/magnesium citrate did not improve participation rate or lesion detection rates, and negatively affected bowel preparation quality.

The quality of colonoscopy preparation in a private clinical practice setting.

No data are available on the quality of the preparation for colonoscopy in private medicine in Spain. We report a retrospective study of the efficacy and tolerability of bowel preparation in the standard clinical practice in a private center.

Impact of patient audiovisual re-education via a smartphone on the quality of bowel preparation before colonoscopy: a single-blinded randomized study.

BACKGROUND AND AIMS: Education on preparation is essential for successful colonoscopy. This study aimed to evaluate the impact of audiovisual (AV) re-education via a smartphone on bowel preparation quality before colonoscopy. METHODS: A prospective, endoscopist-blinded, randomized, controlled study was performed. Patients who underwent colonoscopy with 3 purgatives, including 4 L of polyethylene glycol (4-L PEG), 2 L of PEG with ascorbic acid (2-L PEG/Asc), and sodium picosulfate with magnesium citrate (SPMC), were enrolled and randomized into the AV re-education via smartphone group (AV group, n = 160) and a control group (n = 160). The primary outcome was the quality of the bowel preparation according to the Boston Bowel Preparation Scale (BBPS). The secondary outcomes included instruction adherence using adherence score (AS) and patient satisfaction with education using a visual analog scale (VAS). RESULTS: A total of 283 patients (AV group, n = 139; control group, n = 144) were analyzed per protocol. The mean BBPS (7.53 vs 6.29, P < .001) and the proportion with adequate preparation were higher in the AV group. The mean BBPS of the AV group was significantly higher than that of the control group for the 2-L PEG/Asc and SPMC preparations, but not for the 4-L PEG preparation. The mean AS and the mean VAS score were all significantly higher in the AV group. Among the 3 purgatives, the mean AS was lowest in the 4-L PEG group (P = .041). CONCLUSIONS: AV re-education via smartphone was easy and convenient, and enhanced preparation quality, patient adherence to instructions, and patient satisfaction.

Efficacy and Safety of Sodium Picosulfate/Magnesium Citrate for Bowel Preparation in a Physically Disabled Outpatient Population: A Randomized, Endoscopist-Blinded Comparison With Ascorbic Acid-Enriched Polyethylene Glycol Solution Plus Bisacodyl (The PICO-MOVI Study).

BACKGROUND: Because of its volume, adequate bowel preparation remains problematic in physically unfit patients. OBJECTIVE: This study aimed to compare a small-volume sodium picosulfate/magnesium citrate preparation with a 2-L ascorbic acid-enriched polyethylene glycol solution plus bisacodyl. DESIGN: This study has a noninferiority design, assuming that ascorbic acid-enriched polyethylene glycol solution plus bisacodyl is 70% efficacious in achieving an Ottawa score ≤7 and accepting a difference in success rate of <15% with a target enrollment of 146 patients per group. SETTING: This study was conducted in an outpatient department. PATIENTS: Patients referred for diagnostic colonoscopy were randomly assigned. Key exclusion criteria were severe kidney disease, ASA class ≥III, and hospital admission. INTERVENTION: Patients were randomly assigned to receive sodium picosulfate/magnesium citrate or ascorbic acid-enriched polyethylene glycol solution plus bisacodyl according to a split-dose regimen. Patients in the sodium picosulfate/magnesium citrate group received advice on the recommended 4-L fluid intake. Patients in the ascorbic acid-enriched polyethylene glycol solution plus bisacodyl group received 2 bisacodyl tablets 2 days before and advice on the additionally recommended 2-L fluid intake. MAIN OUTCOME MEASURES: To assess bowel-cleansing adequacy, the Ottawa, Aronchick, and Boston scores were used. Colonoscopy quality measures were obtained. Safety was assessed for a 30-day follow-up period. RESULTS: Overall, 341 patients (169 men, mean age 57.0 years; BMI 26.2 kg/m) were included. Comorbidities were present in 76.2% of patients, and 75.4% of patients used medication. An adequate Ottawa score was obtained in 81.4% and 75.8% of patients receiving ascorbic acid-enriched polyethylene glycol solution plus bisacodyl and sodium picosulfate/magnesium citrate (difference of 5.6% (95% CI, -3.5 to -14.6; p = 0.023)), showing noninferiority of the sodium picosulfate/magnesium citrate therapy. Ottawa segmental scores were lower for sodium picosulfate/magnesium citrate in the right and transverse colon. In both groups, successful ileocecal intubation was achieved in 95%. No medication-related adverse events were reported. LIMITATIONS: These results in a physically disabled ambulant population cannot be extrapolated to immobile, hospitalized patients. CONCLUSIONS: Sodium picosulfate/magnesium citrate proved to be noninferior to ascorbic acid-enriched polyethylene glycol solution plus bisacodyl in efficacy and safety. Timing of the colonoscopy and addition of bisacodyl to sodium picosulfate/magnesium citrate warrants further consideration. See Video Abstract at http://links.lww.com/DCR/A461.

[Preventive therapy with mexidol in toxic damage to the heart]. / Preventivnaia terapiia meksidolom toksicheskogo povrezhdeniia serdtsa.

The purpose of this study was to efficacy of mexidol in the prevention of toxic damage to the heart in acute pancreatitis. MATERIAL AND METHODS: The paper presents the results of experimental studies conducted on 30 adult mongrel adult dogs, which simulated acute focal pancreatic necrosis. We studied the influence of mexidol in the complex therapy for changes in the qualitative and quantitative composition of the lipid tissue structures of the heart, the intensity of processes of lipid peroxidation, antioxidant capacity, phospholipase A2 activity and morphofunctional state of the heart muscle in experimental acute focal pancreatic necrosis. Th. RESULTS AND DISCUSSION: The preventive use of antioxidant drug mexidol in complex treatment of acute focal pancreatic necrosis, which limits the development of endogenous intoxication, increased intensity of lipid peroxidation and restores antioxidant capacity, reduces leading to phospholipase activity in tissue structures of the heart, corrigiruet lipid metabolism and morphofunctional state of the heart, and, consequently, toxic damage to the heart during endotoxic.

Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis.

OBJECTIVE: To compare efficacy of pharmacotherapies for chronic idiopathic constipation (CIC) based on comparisons to placebo using Bayesian network meta-analysis. DATA SOURCES: We conducted searches (inception to May 2015) of MEDLINE, EMBASE, Scopus and Cochrane Central, as well as original data from authors or drug companies for the medications used for CIC. STUDY SELECTION: Phase IIB and phase III randomised, placebo-controlled trials (RCT) of ≥4 weeks' treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least one of four end points. DATA EXTRACTION AND SYNTHESIS: Two investigators independently evaluated all full-text articles that met inclusion criteria and extracted data for primary and secondary end points, risk of bias and quality of evidence. OUTCOMES: Primary end points were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary end points were change from baseline (Δb) in the number of SBM/week and Δb CSBM/week. RESULTS: Twenty-one RCTs (9189 patients) met inclusion and end point criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All prespecified end points were unavailable in four polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week end point. No drug was superior at improving the primary end points on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary end point, Δb in number of SBM/week. CONCLUSIONS: Current drugs for CIC show similar efficacy. Bisacodyl may be superior to prescription medications for Δb in the number of SBM/week in CIC.

Lack of benefit of active preparation compared with a clear fluid-only diet in small-bowel visualization for video capsule endoscopy: results of a randomized, blinded, controlled trial.

BACKGROUND AND AIMS: Controversy remains regarding the type and amount of precapsule bowel cleansing required for small-bowel video capsule endoscopy (VCE). This study aims to assess the efficacy and tolerance of 2 active preparations and a control group of clear fluids only. METHODS: Patients with clinical indications for VCE were randomized to (1) clear fluids only the evening before VCE, (2) 2 sachets of sodium picosulfate plus magnesium sulfate (P/MC) the evening before, or (3) 2 L of polyethylene glycol (PEG) the evening before. Diet instructions were the same for all 3 groups. Small-bowel cleansing was assessed in 3 ways: a 5-point ordinal scale (primary outcome), the percentage of time the small-bowel view was clear, and a validated computerized assessment of cleansing. RESULTS: In total, 198 patients were randomized and 175 patients completed the trial with a mean age of 49.2 years. There was no clear benefit of active preparation with either P/MC or PEG over clear fluids only in the overall 5-point rating scale or in the distal fourth of each examination. There was no difference in diagnostic yield between groups. Significant differences were seen concerning tolerance of the preparations, with a higher proportion rating it as easy or very easy in the clear fluids-only group (93%) and the P/MC group (67%) than in the PEG group (13%) (P < .0001). CONCLUSIONS: Small-bowel cleansing for VCE remains a controversial topic. This randomized control trial demonstrates no benefit in overall or distal small-bowel visualization with active preparation using either PEG or P/MC compared with clear fluids only. (Clinical trial registration number: NCT00677794.).

A head-to-head comparison of 4-L polyethylene glycol and low-volume solutions before colonoscopy: which is the best? A multicentre, randomized trial.

PURPOSE: The purpose of this study is to compare the efficacy and tolerability of polyethylene glycol (PEG) to sodium picosulfate/magnesium citrate (SPMC) and low-volume polyethylene glycol/ascorbic acid (PEGA) in a single- or split-dose regimen for colonoscopy bowel preparation. METHODS: This was a prospective, randomized, endoscopist-blinded, multicentre study. Outpatients received either PEG or SPMC or PEGA in a single or a split dose before the colonoscopy. Quality and tolerability of the preparation and complaints during preparation were recorded. RESULTS: Nine hundred seventy-three patients were analysed. Satisfactory bowel cleansing (Aronchick score 1 + 2) was more frequent when a split dose was used irrespective of the solution type (PEG 90.1 vs 68.8%, PEGA 86.0 vs 71.6%, SPMC 84.3 vs 60.2%, p < 0.001). SPMC was the best tolerated followed by PEGA (p < 0.006) and PEG as the worst (p < 0.001). Tolerability did not correlate with the regimen and amount of the solution used. Female gender is associated with a higher incidence of nausea, vomiting and pain (p < 0.029). CONCLUSIONS: Both PEG, PEGA and SPMC are fully comparable in terms of colonic cleansing when used in similar regimens. The split-dose preparation is more effective in all agents. SPMC and PEGA are better tolerated than PEG. The preparation regimen and/or the volume do not affect tolerability.

Split-Dose Preparations Are Superior to Day-Before Bowel Cleansing Regimens: A Meta-analysis.

BACKGROUND & AIMS: There are different regimens of preparing the colon for colonoscopy, including polyethylene glycol (PEG), sodium phosphate, picosulfate, or oral sulfate solutions. We performed a meta-analysis to determine the efficacy of split-dose vs other colon preparation regimens, the optimal products for use, and the most effective preparation volumes. METHODS: We performed systematic searches of MEDLINE, EMBASE, Scopus, CENTRAL, and ISI Web of knowledge databases, from January 1980 to March 2014, for published results from randomized trials that assessed split-dose regimens vs day-before colonoscopy preparation. We excluded studies that included pediatric or hospitalized patients, or patients with inflammatory bowel disease. The primary outcome was efficacy of bowel cleansing. Secondary outcomes included side effects or complications, outcomes of procedures, patients' willingness to repeat the procedure, and the amount of time required for patients to resume daily activities. RESULTS: We identified 47 trials that fulfilled our inclusion criteria (n = 13,487 patients). Split-dose preparations provided significantly better colon cleansing than day-before preparations (odds ratio [OR], 2.51; 95% confidence interval, 1.86-3.39), as well as day-before preparations with PEG (OR, 2.60; 95% confidence interval, 1.46-4.63), sodium phosphate (OR, 9.34; 95% confidence interval, 2.12-41.11), or picosulfate (OR, 3.54; 95% confidence interval, 1.95-6.45). PEG split-dose preparations of 3 L or more yielded greater bowel cleanliness than lower-volume split-dose regimens (OR, 1.89; 95% confidence interval, 1.01-3.46), but only in intention-to-treat analysis. A higher proportion of patients were willing to repeat split-dose vs day-before cleansing (OR, 1.90; 95% confidence interval, 1.05-3.46), and low-volume split-dose preparations vs high-volume split-dose preparation (OR, 4.95; 95% confidence interval, 2.21-11.10). There were no differences between preparations in other secondary outcome measures. However, there was variation among studies in definitions and main and secondary outcomes. CONCLUSIONS: Based on meta-analysis, split-dose regimens increase the quality of colon cleansing and are preferred by patients compared with day-before preparations. Additional research is required to evaluate oral sulfate solution-based and PEG low-volume regimens further.

Split-dose sodium picosulfate-magnesium citrate colonoscopy preparation achieves lower residual gastric volume with higher cleansing effectiveness than a previous-day regimen.

BACKGROUND AND AIMS: It is known that sodium picosulfate-magnesium citrate (SPMC) bowel preparations are effective, well tolerated and safe, and that split-dosing is more effective for colon cleansing than previous-day regimens. Anesthetic guidelines consider that residual gastric fluid is independent of clear liquid fasting times. However, reluctance to use split-dosing persists. This may be due to limited data on residual gastric fluid volumes (RGFVs) and split-dosing bowel preparations, and that these may not be perceived as standard clear liquids. Furthermore, no studies are available on RGFV/residual gastric fluid pH (RGFpH) and SPMC. We aimed to evaluate the cleansing effectiveness and the RGFV/RGFpH achieved after an SPMC split-dosing regimen compared with a SPMC previous-day regimen. METHODS: This was a single-center observational study. A total of 328 outpatients scheduled for simultaneous EGD and colonoscopy and following a split-dosing or previous-day regimen of SPMC were included. We prospectively measured colon cleanliness by using the Ottawa Bowel Preparation Scale, RGFV, and RGFpH. RESULTS: Ottawa Bowel Preparation Scale scores for overall, right, mid-colon, and colon fluid were significantly better in the split-dosing group. In the split-dosing group, the 3- to 4-hour fasting time consistently achieved the best cleansing quality. RGFV was significantly lower in the split-dosing group (11.09 vs 18.62, P < .001). No significant differences in RGFpH were detected. CONCLUSIONS: Split-dosing SPMC provides higher colon cleansing quality with lower RGFVs than previous-day SPMC regimens. SPMC in split-dosing acts exactly as a standard clear liquid acts, and thus anesthetic guidelines on this issue may be applied with no concerns.

Observational multicentric study to evaluate efficacy, adverse effects and acceptance of bowel cleansing prior to colonoscopy with sodium picosulfate / magnesium citrate formulation CitraFleet®.

The various efficient methods available for bowel preparation prior to colonoscopy differ in patient acceptance. Combining the laxative sodium picosulfate with hyperosmotic magnesium citrate, used in this study in the formulation CitraFleet(®), allows the uptake of the purgative substances as a solution of low volume. This observational study with 737 patients evaluated efficacy of bowel preparation, potential side or adverse effects and patient acceptance of this medicinal product when used by resident physicians in Germany.Colon cleansing with CitraFleet(®) was considered very good to sufficient in 95.2 % of the patients and inadequate in only 4.8 %. In 75 % of the colonoscopies, bowel preparation was rated very good or good. Compared to the standard regimen of two portions taken the day before endoscopy, cleaning efficacy was better when patients received one of the doses on the morning of the day of colonoscopy. The quality of bowel preparation was rated lower by gastroenterologists without any prior experience with sodium picosulfate/magnesium citrate. The overall assessment of the colon cleansing procedure by the 76 participating physicians was very positive and patient acceptance was also very high which can be considered a clear advantage over alternative methods. Efficacy of colon cleansing with CitraFleet(®) was not substantially affected by typical deviations from the recommended standard procedure, emphasizing the robustness of the method. Only one of the patients reported a mild adverse effect potentially caused by the cleansing agents.

[Comparison of colon-cleansing methods in preparation for colonoscopy-comparative of solutions of mannitol and sodium picosulfate]. / Estudio comparativo entre el uso de manitol y el picosulfato sódico como preparación para colonoscopía.

OBJECTIVES: The purpose of the present study is to compare intestinal preparation with mannitol and sodium picosulphate, assessing patient's acceptance, side effects and cleaning capacity. MATERIAL AND METHODS: This is a prospective, nom randomized, blind study, in which the evaluator had no information about the preparation applied. The sample obtained was divided into two groups according to the bowel preparation applied, with 153 patients prepared with 10% mannitol and 84 patients with sodium picosulfate. The evaluation of colon preparation was done using the Boston Scale (Boston Bowel Preparation Scale - BBP) through a three-point scoring system for each of the three regions of the colon: right, left and transverse colon. RESULTS: Of the 237 patients that were evaluated, 146 (61.60%) were female and 91 (38.4%) were male. Regarding the group that used mannitol, 98 were female (64.05%) and 55 were male (35.95%). Among the patients who used sodium picosulfate, 48 were female (57.14%) and 36 were male (42.86%), with no statistical differences between both groups (p> 0.32). Considering that an adequate preparation scores ≥ 6 in the Boston Scale, the bowel cleansing preparation was satisfactory in both groups. 93% of the patients who used mannitol and 81% of the patients who used sodium picosulfate had adequate preparation (score of ≥ 6). Moreover, we consider that the average score in the preparation with Mannitol was 9, while the sodium picosulfate score was 7. There were no significant differences between the two groups. CONCLUSION: There is consensus among authors who state that colonoscopy's safety and success are highly related to the cleansing outcome, regardless of the method used. The same can be observed in the present study, on which both preparations were proved safe and effective for bowel cleansing, according to the Boston scale, as well as accepted by patients and free of complications.

A small molecular agent YL529 inhibits VEGF-D-induced lymphangiogenesis and metastasis in preclinical tumor models in addition to its known antitumor activities.

BACKGROUND: The lymph node metastasis is a key early step of the tumor metastatic process. VEGFD-mediated tumor lymphangiogenesis plays a key role, since down-regulation of p-VEGFR-3 could block the lymph node metastasis. YL529 has been reported to possess potent anti-angiogenesis and antitumor activities; however, its roles in tumor-associated lymphangiogenesis and lymphatic metastasis remain unclear. METHOD: We investigated the effect of YL529 on tumor-associated lymphangiogenesis and lymph node metastasis using in vitro lymph node metastasis models and in vivo subcutaneous tumor models in C57 BL/6 mice. RESULT: We found that YL529 inhibited VEGF-D-induced survival, proliferation and tube-formation of Human Lymphatic Endothelial Cells. Furthermore, in established in vitro and in vivo lymph node metastasis models using VEGF-D-LL/2 cells, YL529 significantly inhibited the tumor-associated lymphangiogenesis and metastasis. At molecular level, YL529 down-regulated p-VEGFR-3, p-JNK and Bax while up-regulated Bcl-2. CONCLUSION: YL529 provided the therapeutic benefits by both direct effects on tumor cells and inhibiting lymphangiogenesis and metastasis via the VEGFR-3 signaling pathway, which may have significant direct clinical implications.

Predicting inadequate bowel preparation for colonoscopy in participants receiving split-dose bowel preparation: development and validation of a prediction score.

BACKGROUND: Adequate bowel preparation is important for optimal colonoscopy. It is important to identify patients at risk for inadequate bowel preparation because this allows taking precautions in this specific group. OBJECTIVE: To develop a prediction score to identify patients at risk for inadequate bowel preparation who may benefit from an intensified bowel cleansing regimen. DESIGN: Patient and colonoscopy data were prospectively collected, whereas clinical data were retrospectively collected for a total of 1996 colonoscopies in participants who received split-dose bowel preparation. Multivariate logistic regression analyses were conducted in a random two-thirds of the cohort to develop a prediction model. Validation and evaluation of the discriminative power of the prediction model were performed within the remaining one-third of the cohort. SETTING: Four centers, including one academic and three medium-to-large size nonacademic centers. PATIENTS: Consecutive colonoscopies in November and December 2012. Mean age was 57.3 ± 15.9 years, 45.8% were male and indications for colonoscopy were screening and/or surveillance (27%), abdominal symptoms and/or blood loss and/or anemia (60%), inflammatory bowel disease (9%), and others (4%). INTERVENTIONS: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Inadequate bowel preparation defined as Boston Bowel Preparation Scale score <6. RESULTS: A total of 1331 colonoscopies were included in the development cohort, of which 172 (12.9%) had an inadequate bowel preparation. Independent factors included in the prediction model were American Society of Anesthesiologists Physical Status Classification System score ≥3, use of tricyclic antidepressants, use of opioids, diabetes, chronic constipation, history of abdominal and/or pelvic surgery, history of inadequate bowel preparation, and current hospitalization. The discriminative ability of the scale was good, with an area under the curve of 0.77 in the validation cohort. LIMITATIONS: Study design partially retrospective, no data on patient compliance. CONCLUSION: We developed a validated, easy-to-use prediction scale that can be used to identify subjects with an increased risk of inadequate bowel preparation with good accuracy.

A randomized trial to compare the efficacy and tolerability of sodium picosulfate-magnesium citrate solution vs. 4 L polyethylene glycol solution as a bowel preparation for colonoscopy.

PURPOSE: The purpose of this study is to compare the efficacy and acceptability of an evening-before regimens of sodium picosulfate/magnesium citrate (SPMC) and polyethylene glycol (PEG) as bowel cleansers and to explore the results of a same-day regimen of SPMC. METHODS: Multicenter, randomized, observer-blinded, parallel study carried out in subjects who were 18-80 years old and were undergoing diagnostic colonoscopy for the first time. The primary outcome was treatment success, which was a composite outcome defined by (1) the evaluation of the overall preparation quality as "excellent" or "good" by two blinded independent evaluators with the Fleet(®) Grading Scale for Bowel Cleansing and (2) a subject's acceptability rating of "easy to take" or "tolerable." The primary outcome was analyzed using a logistic regression with site, gender, and age group (age ≥65 years and <65 years) as factors. RESULTS: Four hundred ninety subjects were included in the efficacy evaluation. Although treatment success was significantly higher in subjects assigned to the evening-before regimen of SPMC vs. subjects assigned to the evening-before PEG, when evaluating the two individual components for treatment success, there were significant differences in the ease of completion but not in the quality of preparation. The same-day SPMC regimen was superior to both the evening-before regimen of SPMC and PEG in terms of the quality of preparation, especially regarding the proximal colon. CONCLUSIONS: An evening-before regimen of SPMC is superior to an evening-before regimen of PEG in terms of subject's acceptability. The same-day SPMC regimen provides better cleansing levels in the proximal colon.

Randomized controlled trial of low-volume bowel preparation agents for colonic bowel preparation: 2-L polyethylene glycol with ascorbic acid versus sodium picosulfate with magnesium citrate.

PURPOSE: Both 2-L polyethylene glycol with ascorbic acid (2-L PEG/Asc) and sodium picosulfate with magnesium citrate (SP/MC) are low-volume combined agents for colonic preparation. The aim of the current study was to compare the preparation adequacy and patient tolerability of 2-L PEG/Asc and SP/MC. METHODS: We performed a prospective randomized controlled study in outpatients undergoing daytime colonoscopy at a tertiary academic hospital. We compared preparation adequacy based on the Boston Bowel Preparation Scale (BBPS), polyp and adenoma detection rate (PDR and ADR), compliance, tolerability for ease and palatability, intention to reuse, and patient satisfaction using a questionnaire between 2-L PEG/Asc and three sachets of SP/MC, both given in a split-dose method. RESULTS: A total of 388 patients were evaluated based on intention to treat (ITT) and 356 patients per protocol (PP). No significant differences in preparation adequacy were observed in ITT and PP analyses, based on the BBPS (p > 0.05). The PDR and ADR were greater than 60 and 40% in both groups, respectively (p > 0.05). Compliance levels were higher in the 2-L PEG/Asc group than in the SP/MC group (p < 0.001). Satisfaction (ITT, p = 0.014; PP, p = 0.032) and palatability (ITT and PP, p < 0.001) levels were higher in the SP/MC group than in the 2-L PEG/Asc group, but values for tolerability for ease and intention to reuse were similar in both groups (ITT and PP, p > 0.05). CONCLUSIONS: Both 2-L PEG/Asc and SP/MC had adequate bowel cleansing efficacy to satisfy PDR and ADR as quality indicator and had showed similar tolerability.

Single-day sodium picosulfate and magnesium citrate versus split-dose polyethylene glycol for bowel cleansing prior to colonoscopy: A prospective randomized endoscopist-blinded trial.

BACKGROUND AND AIM: The intake of polyethylene glycol (PEG) prior colonoscopy is frequently associated with nausea and abdominal discomfort. The aim of this study was to investigate whether sodium picosulfate and magnesium citrate (PMC) is superior to a polyethylene glycol (PEG) preparation in regard to patient acceptance. Furthermore, it investigates possible differences in efficiency and patient safety. METHODS: In a randomised, prospective, and endoscopist-blinded study patients were 1:1 randomized to either use PMC or 4-L PEG in order to prepare for colonoscopy. Cleansing regimes consisted of a split-dose administration in the PEG arm and standard administration in the PMC arm. Primary end point was proportion of patients evaluating the bowel preparation procedure as "very distressing," defined as ≥ 8 points on a 10-point numeric rating scale (NRS). Secondary end points were quality of bowel preparation and electrolyte parameters. RESULTS: PMC bowel-cleansing procedure was better tolerated compared with PEG (PMC(NRS<8) = 89.9% vs PEG(NRS<8) = 79.2%, P = 0.037). Mean declines in serum sodium (ΔSodium(PEG) = -0.76 ± 3.07 vs ΔSodium(PMC) = -3.38 ± 3.56 mmol/L; P < 0.001), chloride (ΔChloride(PEG) = -1.00 ± 3.22 vs ΔChloride(PMC) = -3.49 ± 3.51 mmol/L; P < 0.001), and osmolality (ΔOsmolality(PEG) = -4.23 ± 6.82 vs ΔOsmolality(PMC) = -8.83 ± 7.43 mosmol/kg; P < 0.001) were higher in the PMC arm than in the PEG arm. Hyponatremia after bowel preparation occurred more often in PMC (21.2%) than in PEG (4.0%) (P < 0.001). Successful preparation was achieved more frequently in the PEG arm (42.9% vs 82.2%; P < 0.001). CONCLUSION: Standard picosulfate/magnesium citrate is better accepted than a split-dose PEG regimen. From the perspective of successful preparation and patients' safety, PEG is superior to PMC.