The effect of gastrointestinal microbiome supplementation on immune checkpoint inhibitor immunotherapy: a systematic review.

PURPOSE: Gastrointestinal (GI) microbiome modulators, such as fecal microbiome transplants (FMTs), are being considered as supplements to standard immune checkpoint inhibitor (ICI) treatment to improve efficacy. This systematic review aims to assess the study design and outcomes of clinical trials that use FMTs to enhance ICI treatment. METHODS: Systematic literature searches were conducted on PubMed and Embase using search terms that included names of ICIs and gastrointestinal microbiome. A first search identified interventional trials, and the second search identified interventional, retrospective, and observational studies. RESULTS: The search for interventional trials produced 205 articles, 3 of which met the inclusion criteria. All studies had sample sizes ranging between 10 and 30 participants. 2 of the studies were single-arm studies with no control arm. One study reported an overall response rate (ORR) of 3 out of 15 (20%), a median progression-free survival (PFS) of 3 months, and a median overall survival (OS) of 7 months. The second study reported 1 complete response out of 10 (10%) and 2 partial responses out of 10 (20%). The third study reported an ORR of 58% vs. 20%, a median PFS of 12.7 months vs. 2.5 months in patients receiving nivolumab-ipilimumab plus CBM588 compared with patients receiving nivolumab-ipilimumab alone respectively, and an undefined median OS. CONCLUSION: Current studies on the microbiome modulators with ICI use are limited in study design. Future clinical trials should be randomized, use larger sample sizes, and use an appropriate control arm to better ascertain the clinical effect of the GI microbiome on ICI treatment.

The AGILE trial of ivosidenib plus azacitidine versus azacitidine alone: How many limitations is too many?

The AGILE trial compared ivosidenib and azacitidine versus azacitidine for IDH1-mutant acute myeloid leukemia (AML) in elderly patients who were ineligible to receive intensive chemotherapy. While the results of this trial appear encouraging, various concerns become evident from the study design and methodology. First, the AGILE trial did not use post-protocol therapy that met the current standard of care. Second, researchers continued patient enrollment despite knowledge of the survival benefit of azacitidine plus venetoclax shown in the VIALE-A trial, resulting in an inferior control arm. Third, the primary endpoint of AGILE was changed from overall survival (OS) to event-free survival (EFS), and the sample size was reduced to expedite the results. Finally, the trial was halted early based on a non-primary endpoint, which likely led to exaggerated effect size or misleading results. We discuss these limitations and continue to advocate for careful analysis of study design to ensure that appropriate and accurate outcomes are implemented in future studies.

Flash Glucose Monitoring in Subjects with Diabetes on Hemodialysis: A Pilot Study.

BACKGROUND: In patients with diabetes related end-stage renal disease (ESRD) on hemodialysis, blood glucose management can be challenging due to the kinetics of glucose and insulin in addition to other factors. The glucose monitoring systems which measure glucose levels continuously may be useful to study the glucose profile of patients with diabetes undergoing hemodialysis. Our study is designed to use ambulatory glucose profile to study the glucose pattern - during, before, and after a session of hemodialysis. MATERIALS AND METHODS: Ten patients with type 2 diabetes with ESRD undergoing hemodialysis were recruited. Forty-eight glucose readings were recorded in a 12-h period which included 4 h each prior, during, and after the dialysis session with a flash glucose monitor (FreeStyle Libre-pro). The same 12 h time frame was also monitored on a non-dialysis day. RESULTS: On the day of dialysis, the mean glucose level was significantly lower (P = 0.013) compared to the day without dialysis (95 ± 12.7 mg/dl vs 194 ± 76.8 mg/dl). As compared to the pre-dialysis period, the mean blood glucose levels during dialysis were lower (P = 0.004). As compared to the dialysis period, the mean blood glucose levels in the post-dialysis period were higher but did not reach statistical significance. CONCLUSION: In our study, subjects with type 2 diabetes on hemodialysis had lower glucose levels on the day of dialysis compared to non-dialysis day. Glucose levels showed a fall during hemodialysis and then a rise to higher levels after dialysis.

Effect of a Low-Calorie Diet on Restoration of Normoglycemia in Obese subjects with Type 2 Diabetes.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is considered to be an inevitably progressive disease. Complex therapies add to the financial and psychological burden. Very low-calorie diets (LCDs) are emerging as an option in the management of type 2 diabetes. METHODS: We performed a clinical audit of patients with T2DM who received 12 weeks of LCD. RESULTS: This case series documents that 6 out of 12 participants (median baseline HbA1c 9%) achieved HbA1c level in nondiabetes range with LCD despite stopping all antidiabetes medications. There was an improvement in serum triglycerides, HDL cholesterol, total cholesterol, C-Reactive protein, urine microalbumin, liver transaminases, liver fat and the indices of insulin resistance, beta cell secretory capacity, and insulin sensitivity. CONCLUSION: If long-term follow-up proves sustained benefits, such dietary restriction may be an alternative to more drastic options for reversal of type 2 diabetes. This may also help in changing the treatment perspective of a newly detected T2DM from an incurable and inevitably progressive disease to a potentially reversible disease.

Antioxidant potential of banana: Study using simulated gastrointestinal model and conventional extraction.

Most reports on fruit antioxidant capacities are based on extraction of antioxidants using polar solvents. In banana, little is known about the fate of bioactive compounds during the digestion process, particularly in the food matrix under the gastric and intestinal conditions. In the present study, an in vitro gastrointestinal digestion method was used to simulate physiological conditions of the stomach and small intestine to evaluate the actual antioxidant capacity of banana. The simulated gastrointestinal extracts showed significantly higher antioxidant properties. The total phenol content of the physiological enzymatic extract was higher by almost 150% than the methanolic extract. Similarly, the flavonoid and flavonol contents were higher in the physiological enzymatic extract by 330.6 and 141.7%, respectively as compared to methanolic extract. These differences were also noticed in the antioxidant capacity measurement parameters. From the results, it can be concluded that the conventional extracts underrate the antioxidant value of banana and that they may have much higher health significance, as an antioxidant in particular.

Gestational diabetes mellitus in rural population of Western India - Results of a community survey.

CONTEXT: Gestational diabetes mellitus (GDM) should be diagnosed early, as untreated maternal hyperglycemia leads to adverse materno-fetal outcome. SUBJECTS AND METHODS: We studied prevalence of gestational diabetes by a house to house survey of a rural population in western India. A cluster of remote villages with little access to health care were chosen. RESULTS: A total of 989 women participated in the study out of which 9.5% (n = 94) were diagnosed as GDM. In a stepwise multivariate regression analysis a higher body mass index during pregnancy was a predictor of gestational diabetes. The prevalence of diabetes was similar in women with gestational age of >24 weeks and <24 weeks, suggesting the need for early screening. CONCLUSIONS: Our results suggest the need for implementing health programs to diagnose and treat gestational diabetes in this population.