Effectiveness and safety of 1-L PEG-ASC versus other bowel preparations for colonoscopy: A meta-analysis of nine randomized clinical trials.

BACKGROUND AND AIMS: A 1-L polyethylene glycol plus ascorbate (PEG-ASC) preparation has been recently developed to improve patients' experience in colonoscopy. This meta-analysis aimed to evaluate the effectiveness and safety of 1-L PEG-ASC compared with those of other bowel preparations for colonoscopy. METHODS: MEDLINE, Embase, Scopus, and the Cochrane Library were systematically searched for randomized controlled trials comparing 1-L PEG-ASC with other bowel preparations published through July 2022. A random-effects model was applied for pooling the results; heterogeneity was expressed as I2. RESULTS: Nine studies met the inclusion criteria and were included. The analysis showed significantly higher cleansing success (CS) (OR = 1.50; 95% CI = 1.25-1.81; p < 0.01, I2 = 0%) and right-colon high-quality cleansing (HQC) (OR = 1.67; 95% CI = 1.21-2.31; p < 0.01, I2 = 43%) with 1-L PEG-ASC compared to the other preparations. The pooled estimate of the adenoma detection rate (ADR) did not significantly differ between the two groups either in the overall (OR = 1.02; 95% CI = 0.87-1.20; p = 0.79, I2 = 0%) or split-dosing regimen subgroup analysis (OR = 0.99; 95% CI = 0.84-1.18; p = 0.94, I2 = 0%). A significantly higher pooled estimate of the number of patients with adverse events (AEs) (OR = 1.51; 95% CI = 1.23-1.84; p<0.01, I2 = 0%) and incidence of AEs (IRR=1.33; 95% CI = 1.11-1.58; p<0.01, I2 = 71%) was observed with 1-L PEG-ASC than with the other preparations. No serious AEs or deaths occurred. CONCLUSIONS: Compared to other preparations, 1-L PEG-ASC yielded higher overall CS, higher right-colon HQC rates, and similar ADR. The number of patients with AEs and incidence of the total AEs were significantly higher with 1-L PEG-ASC in the absence of serious AEs.

Azathioprine for prevention of clinical recurrence in Crohn's disease patients with severe endoscopic recurrence: an IG-IBD randomized double-blind trial.

OBJECTIVE: The recurrence of Crohn's Disease after ileo-colonic resection is a crucial issue. Severe endoscopic lesions increase the risk of developing early symptoms. Prevention and treatment of post-operative Endoscopic Recurrence (ER) have been studied with conflicting results. We compare effi cacy of azathioprine (AZA) vs. high-dose 5-aminosalicylic acid (5-ASA) in preventing clinical recurrence and treating severe post-operative ER. PATIENTS AND METHODS: We performed a 1-year multicenter randomized double-blind double-dummy trial. Primary end-points were endoscopic improvement and therapeutic failure (clinical recurrence or drug discontinuation due to lack of efficacy or adverse events) 12 months after randomization. We also performed a post-trial analysis on symptomatic and endoscopic outcomes 10 years after the beginning of the trial, with a median follow-up of 60 months. RESULTS: Therapeutic failure occurred in 8 patients (17.4%) within 12 months from randomization, with no significant difference between patients treated with 5-ASA (20.8%, 5 patients) and those with AZA (13.6%, 3 patients). Therapeutic failure was due to clinical recurrence in the 5-ASA group and to adverse events in the AZA group. Endoscopic improvement at 12 months was observed in 8 patients, 2 (11.8%) in the 5-ASA group and 6 (30%) in the AZA group. No serious adverse event was recorded. At the post-trial analysis (median follow-up 60 months), 47.8% (22/46) of patients experienced clinical recurrence: 54.2% (13/24) in the 5-ASA group and 40.9% (9/22) in the AZA group, p=0.546. Patients treated with AZA had lower risk of drug escalation. Clinical recurrence was associated with smoking (p=0.031) and previous surgery (p=0.003). CONCLUSIONS: Our trial indicates that there was no difference in terms of treatment failure between 5-ASA and AZA in patients with severe ER. The main limit of AZA is its less favorable safety profile.

Effectiveness and safety of NER1006 versus standard bowel preparations: A meta-analysis of randomized phase-3 clinical trials.

BACKGROUND: A 1 L PEG-based preparation for colonoscopy (NER1006) has been recently developed. AIMS: We conducted a meta-analysis of randomized controlled trials (RCTs) to explore the effectiveness and safety of NER1006 versus traditional preparations. METHODS: PubMed/Medline and Embase were systematically searched through January 2020 for phase-3 RCTs comparing NER1006 versus standard preparations. RESULTS: Three RCTs (1879 participants) met the inclusion criteria and were included. The analysis showed a higher cleansing success for NER1006 compared standard preparations (OR=1.28; 95% CI 1.00-1.62; p = 0.047, I2=0%) as well as a greater high-quality cleansing of the right colon (OR=2.13; 95% CI 1.16-3.94; p = 0.015, I2=76.0%) when assessed by the Harefield Cleansing Scale (HCS). The pooled estimate of the NER1006 effect on ADR showed a higher, although not significant, ADR of the right colon (OR=1.19; 95% CI 0.73-1.92; p = 0.485, I2=53%). When considering the impact of NER1006 on mild to moderate treatment-emergent adverse events (TEAEs), we observed a significant pooled estimate of TEAEs (OR=2.31; 95% CI 1.82-2.94; p<0.001, I2=0%). CONCLUSIONS: When compared to traditional preparations, NER1006 showed a better overall cleansing of the colon as well as a greater high-quality cleansing of the right colon, with comparable ADR. A higher incidence of mild to moderate TEAEs was observed for NER1006, in the absence of serious adverse events.

Human pregnancy is accompanied by modifications in B cell development and immunoglobulin profile.

Though human pregnancy success has been classically linked with a shift into a Th2 immunoglobulin producing cell response, a clear picture concerning B cell development and immunoglobulin profile during human pregnancy is missing. We analyzed in this work the dynamic of different B cell populations in peripheral blood of pregnant women on the first, second and third trimester of pregnancy. As control, age-matched non-pregnant fertile women were included. Additionally, we quantified the levels of immunoglobulin (IgG1, IgG2, IgG3, IgG4, IgM, IgA and IgE) in the serum of pregnant and non-pregnant women. We observed a significant decrease in the percentages of transitional B cells in peripheral blood of pregnant women as compared to non-pregnant control women. Besides, percentages of naïve as well as switched and non-switched memory B cells in peripheral blood of pregnant women were similar to those in non-pregnant control women. Interestingly, although we did not observe differences in the activation status of B cells as well as in the percentages of plasma cells between pregnant and non-pregnant women, we observed significantly higher levels of IgM, IgA, IgG3, more likely natural antibodies, as well IgG4 in serum of pregnant women compared to non-pregnant age matched control women.

Age does not adversely influence outcomes among patients older than 60 years who undergo allogeneic hematopoietic stem cell transplant for AML and myelodysplastic syndrome.

Allogeneic hematopoietic stem cell transplant (AHSCT) outcomes data of older AML/myelodysplastic syndrome (MDS) patients are limited. We retrospectively evaluated consecutive patients ⩾60 years old with AML/MDS who underwent AHSCT between January 2005 and December 2014. The primary objectives were to determine nonrelapse mortality (NRM), relapse, relapse-free survival (RFS) and overall survival (OS) at 1 year post AHSCT. A total of 159 patients underwent AHSCT with a median age of 64 (range, 60-75) years. Of these, 103 patients (65%) had AML and 56 patients (35%) had MDS. At 1 year post AHSCT, grade III-IV acute GvHD and chronic GvHD occurred in 20.8% (95% confidence interval (CI), 14.9-27.5%) and 54.1% (95% CI, 46.0-61.5%) of patients, respectively. NRM, RFS, relapse rate and OS at 1 year post AHSCT were 25.3% (95% CI, 18.8-32.3%), 53.3% (95% CI, 46.1-61.7%), 21.4% (95% CI, 15.4-28.1%) and 56.4% (95% CI, 49.2-54.7%), respectively. High disease risk index was associated with poor RFS, OS and higher relapse rate (P<0.03), whereas non-thymoglobulin-based GvHD prophylaxis, higher comorbidity index (⩾3) and MDS were associated with higher NRM (P<0.03). Importantly, age did not have an adverse effect on NRM, relapse, RFS and OS. AHSCT was well tolerated. Hence, older age alone should not be considered a contraindication to AHSCT.

Low-dose antithymocyte globulin enhanced the efficacy of tacrolimus and mycophenolate for GVHD prophylaxis in recipients of unrelated SCT.

We performed a retrospective analysis of the outcome of 197 consecutive unrelated donor transplant recipients who received GVHD prophylaxis either TM regimen (tacrolimus and mycophenolate) (121 patients) or TM/ATG-G regimen (TM with low-dose antithymocyte globulin (ATG) of 4.5 mg/kg, ATG-G, Genzyme) (76 patients). Cumulative incidences of grade II-IV acute GVHD for the TM and TM/ATG-G cohorts were 49% and 61% (P=0.11) and grade III-IV acute GVHD for the TM and TM/ATG-G cohorts were 27% and 14% (P=0.02), respectively. There was no difference in the incidence of relapse or disease progression between TM and TM/ATG-G-16% and 23% (P=0.64). TM/ATG-G cohort had lower incidence of non-relapse mortality (NRM; 37% vs 20%, P=0.01), chronic GVHD (56% vs 43%, P<0.001) and more favorable global chronic GVHD severity (P<0.001). Univariate analyses showed improved OS and PFS of patients who received TM/ATG-G. Multivariate analysis confirmed TM/ATG-G had a favorable influence on OS (P=0.05) but not on PFS (P=0.07). We concluded that low-dose ATG of 4.5 mg/kg given in conjunction with TM improved GVHD prophylaxis without increased risk of relapse. Lower NRM, lower incidence and severity of chronic GVHD could potentially improve survival.