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Cesar A Arias

Publications and source records attributed to Cesar A Arias.

4 recordsLinked to original sources

First-line fecal microbiota transplantation for the management of immune checkpoint inhibitor-mediated diarrhea and colitis.

Immune checkpoint inhibitor (ICI) therapy commonly leads to adverse events such as ICI-mediated diarrhea and colitis (IMDC). Fecal microbiota transplantation (FMT) remains an option for patients with refractory colitis. We report a multi-omics profiling of patients receiving first-line FMT for IMDC. In our preliminary analysis, 10 (76.9%) patients achieve clinical response, with a median time to clinical improvement of 1.5 (1-10.5) days. Among responder patients with baseline and follow-up samples, 6 (75%) show an increase in alpha-diversity post-FMT. Pre-FMT samples show an increase in the abundance scores of plasma cells, neutrophils, macrophages (M1 and M2), memory activated and resting memory CD4+ T cells, CD8+ T cells, T follicular helper (Tfh) cells, and regulatory T cells (Tregs), all of which decrease post-FMT. In a small cohort of patients, we identify potential mechanisms for FMT response and demonstrate that first-line FMT in patients with IMDC (NCT04038619) can be effective.

FMT

A Duty to Act.

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healthcare

A Duty to Act.

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healthcare

Loss of O-antigen due to wbbL mutations is common and associated with increased mortality in Escherichia coli bloodstream infections.

Escherichia coli bloodstream infections are common and associated with high mortality. A key feature of E. coli is the lipopolysaccharide (LPS) O-antigen, which contributes to immune evasion during invasive infection. We analyzed serial isolates from patients with relapsed E. coli bacteremia and identified frequent disruption of O-antigen synthesis due to mutations in wbbL, resulting in a rough LPS phenotype. Rough LPS isolates were more serum sensitive and less pathogenic in mice. Despite this apparent attenuation, 11 of 61 (18%) E. coli sequence type 131 bloodstream isolates in our cohort harbored disruptive wbbL mutations and were associated with significantly worse clinical outcomes, including septic shock and mortality. Using a murine model of recurrent bacteremia, we show that rough LPS isolates partially evade protective immunity generated against smooth LPS E. coli, highlighting the importance of host immune context in invasive disease.

O Antigens