Modeling of the Biological Activity of Monoclonal Antibodies Based on the Glycosylation Profile.

The influence of the glycosylation profile of IgG on biological activity is known, but it is not clear which glycoforms have the highest impact on the main mechanism of action. The aim of this study was to design a mathematical model for predicting the antibody-dependent cellular cytotoxicity (ADCC) activity and the Fc gamma IIIa receptors' (FcɣRIIIa) relative binding of rituximab drug products based on their glycosylation profile. An additional goal was to identify the glycoforms that have the greatest impact on these mechanisms of action. For these purposes, the glycosylation profile was examined by hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC), ADCC was assessed using a Promega kit, and FcɣRIIIa's binding affinity was assessed by surface plasmon resonance (SPR) analysis of a group of >50 rituximab drug products. Based on the results, mathematical models for the ADCC and FcɣRIIIa binding affinity prediction were designed using JMP 13.2.0. The quality of the model and the influence of sample size and heterogeneity on the reliability were verified. The results allow for the evaluation of rituximab drug products' activity based on their glycosylation profile and show that with a sufficiently large and differentiated dataset, it is possible to generate models for different monoclonal antibodies.

Efficacy of probiotics in patients with morbid obesity undergoing bariatric surgery: a systematic review and meta-analysis.

Bariatric surgery is considered effective for morbid obesity, and probiotic supplementation might provide some benefits. We aimed to revise the evidence regarding probiotic supplementation in patients with morbid obesity undergoing bariatric surgery. MEDLINE, Embase, Web of Science, CENTRAL, and trial registers were searched up to April 1, 2020. We included randomized controlled trials and controlled clinical trials, and outcomes of interest were weight change, quality of life, gastrointestinal symptoms, and adverse events. All stages of the review were done by 2 authors independently and we followed Cochrane Handbook guidance. We screened 2541 references and included 5 studies. Probiotics may have minor to no effect regarding percentage excess weight loss (%EWL) at 6 weeks (mean difference [MD], .28; 95% CI, -9.53 to 10.09; 44 participants, 2 studies), 3 months (MD, 5.47; 95% CI, -3.22 to 14.17; 165 participants, 3 studies), 6 months (MD, .46; 95% CI, -8.14 to 9.07; 115 participants, 2 studies), and 12 months post surgery (MD, .35; 95% CI, -8.66 to 9.37; 123 participants, 2 studies). We observed short-term improvement in gastrointestinal symptoms. There was no important effect on quality of life and no meaningful adverse events. Because probiotic supplementation might provide some benefit with respect to weight loss, might alleviate some gastrointestinal symptoms, and is associated with minor or no adverse events, continuous supplementation might be worth considering in certain individuals. Our findings are based on the body of evidence of very low certainty, and further well-designed randomized controlled trials are required to elucidate the effect and strengthen the certainty in the estimates.

Systematic review and meta-analysis of perioperative behavioral lifestyle and nutritional interventions in bariatric surgery: a call for better research and reporting.

Bariatric surgery is considered the most effective treatment for people with morbid obesity, and certain interventions could enhance its long-term results. We searched MEDLINE, Embase, Web of Science, CENTRAL, and trial registers up to January 1, 2020. Randomized controlled trials, where behavioral lifestyle or nutritional interventions were provided perioperatively were included. Primary outcome was weight change. Two reviewers independently performed each stage of the review. Altogether 6652 references were screened. 31 studies were included for qualitative synthesis and 22 studies for quantitative synthesis. Interventions varied greatly, thus limiting possibility of synthesizing all results. Six groups of interventions were discerned, and we used standardized mean differences for synthesis. Low to very-low certainty evidence suggests that physical activity, nonvitamin nutritional interventions, vitamins, psychotherapy, and counseling but not combined interventions might bring some benefit regarding short-term postsurgery follow-ups (up to 12 mo), but the estimates varied and results were not statistically significant, except for 12 months follow-ups regarding counseling. Psychotherapy and counseling, but not vitamins and combined interventions, may provide some benefit at longer follow-ups (over 12 mo), but the certainty of evidence was low to very-low and statistically significant results were observed in comparisons including data from single studies with small sample sizes only. Included studies expressed an outcome "weight change" using 20 different measures. Misreporting of data and huge variety of outcomes do not benefit systematic analyses and may possibly lead to confusion of both researchers and readers. We suggest that authors follow a predefined set of outcomes when reporting the results of their studies. The initiative to produce "core outcome set" for clinical trials in bariatric surgery trials is currently underway.