Understanding of the importance of the normal intestinal microbial community in regulating microbial homeostasis, host metabolism, adaptive immune responses, and gut barrier functions has opened up the possibility of manipulating the microbial composition to modulate the activity of various intestinal and systemic diseases using fecal microbiota transplant (FMT). It is therefore not surprising that use of FMT, especially for treating relapsed/refractory Clostridioides difficile infections (CDI), has increased over the last decade. Due to the complexity associated with and treatment for these diseases, patients with hematologic and oncologic diseases are particularly susceptible to complications related to altered intestinal microbial composition. Therefore, they are an ideal population for exploring FMT as a therapeutic approach. However, there are inherent factors presenting as obstacles for the use of FMT in these patients. In this review paper, we discussed the principles and biologic effects of FMT, examined the factors rendering patients with hematologic and oncologic conditions to increased risks for relapsed/refractory CDI, explored ongoing FMT studies, and proposed novel uses for FMT in these groups of patients. Finally, we also addressed the challenges of applying FMT to these groups of patients and proposed ways to overcome these challenges.
BackgroundMany co-existing medical conditions may affect the outcome in patients treated with immune checkpoint inhibitors for advanced cancer. There is currently not any information on whether metabolic syndrome (MetS) impacts the clinical outcome in patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell line cancer (NSCLC).MethodsWe carried out a single-center retrospective cohort study to determine the effects of MetS on first-line ICI therapy in patients with NSCLC.ResultsOne hundred and eighteen consecutive adult patients who received first-line therapy with ICIs and had adequate medical record information for the determination of MetS status and clinical outcomes were included in the study. Twenty-one patients had MetS and 97 did not. There was no significant difference between the two groups in age, gender, smoking history, ECOG performance status, tumor histologic types, pre-therapy use of broad-spectrum antimicrobials, PD-L1 expression, pre-treatment neutrophil:lymphocyte ratio, or proportions of patients who received ICI monotherapy or chemoimmunotherapy. With a median follow-up of 9 months (range 0.5-67), MetS patients enjoyed significantly longer overall survival (HR 0.54, 95% CI: 0.31-0.92) (p = 0.02) but not progression-free survival. The improved outcome was only observed in patients who received ICI monotherapy and not chemoimmunotherapy. MetS predicted for higher probability of survival at 6 months (p = 0.043) and 12 months (p = 0.008). Multivariate analysis indicated that, in addition to the known adverse effects of use of broad-spectrum antimicrobials and the beneficial effects of PD-L1 (Programmed cell death-ligand 1) expression, MetS was independently associated with improved overall survival but not progression-free survival.ConclusionsOur results suggest that MetS is an independent predictor of treatment outcome in patients who received first-line ICI monotherapy for NSCLC.
Many broad-spectrum antibiotics (BSA) alter the intestinal microbiome that regulates adaptive immune responses. We hypothesized that BSA use before and early after kidney transplant may affect acute graft rejection (AGR). We carried out a retrospective cohort study on all patients who underwent kidney transplants in our institution. Patient demographics, clinical data, diagnosis, and treatment history were collected. Antibiotic use within 2 months prior to transplant and during the hospital admissions for transplant, as well as antibiotic types were recorded. A total of 357 consecutive first transplants were included for analysis. Median age was 52 years (range 7–76). A total of 67 patients received living donor and 290 deceased donor kidneys. A total of 19 patients received BSA within two months prior to transplant and 55 patients during the hospital admission for the transplant. With a median follow-up of 1270 days, 38 episodes of biopsy-proven AGR were recorded. There was no difference in the AGR rates during the first year between patients who received BSA and those who did not. However, the use of piperacillin/tazobactam or meropenem (PM) was associated with increased risks for the development of AGR, irrespective of the source of the donor grafts. Time to development of AGR was also shorter. Our data, therefore, suggest that the use of PM BSA prior to and immediately after kidney transplant increases the risks for AGR.
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