Rifaximin is a poorly water-soluble and minimally absorbed (<0.4%) rifamycin with in vitro activity against enteric Gram-negative bacteria including enteric pathogens. Fecal levels of the drug after 3 days' oral therapy exceed 8000 microg/g. Rifaximin is effective in the treatment and prevention of travelers' diarrhea due to Escherichia coli-predominant bacterial pathogens. It shows lower activity against dysenteric forms of bacterial diarrhea. The drug may be useful in other enteric infectious diseases, including Clostridium difficile colitis, pediatric bacterial diarrhea and Helicobacter pylori gastritis and chronic gastrointestinal disorders including hepatic encephalopathy, small bowel bacterial overgrowth, inflammatory-bowel disease, irritable-bowel syndrome and pouchitis. Importantly, rifaximin does not appear to lead to bacterial resistance. Rifaximin has an excellent safety profile and adverse drug reactions have been comparable to those associated with the placebo control agent.

Diarrhea was prevalent in 12.4% of hospitalized patients at a large university hospital at one point in time. Patients with diarrhea were more likely to have CD infection, receive antibiotics, or experience a longer hospitalization. Half of the CD diarrhea cases occurring in the hospital had been previously unidentified. Hospitalized patients should be evaluated for diarrhea on an ongoing basis with appropriate interventions instituted.

Introduction: Gastroenteropancreatic neuroendocrine carcinomas (GEPNEC) are characterised by a heterogeneous molecular profile and a poor prognosis. Circulating tumour DNA (ctDNA) analysis may be useful for NEC management. This study aimed at describing ctDNA mutations, to assess their predictive value for response to chemotherapies, and their change according to disease progression. Methods: The CIRCAN-NEC study included patients with GEPNEC or NEC from an unknown primary, scheduled to begin first or second-line chemotherapy. Blood samples were collected prior to chemotherapy initiation, at first evaluation, and during disease progression. ctDNA were sequenced by next-generation sequencing (NGS). Molecular response was defined as a decrease of at least 30% of the mutant allele fraction (MAF). Results: All 24 patients included received platinum-etoposide first-line chemotherapy; 19 received a FOLFIRI-based post first-line regimen. Twenty-two patients had at least one driver mutation: TP53 (n=21), RB1 (n=2), KRAS (n=4), BRAF (n=3). Ten (42%) had a “adenocarcinoma-like” profile. Five of six patients with matching ctDNA/tissue NGS harboured at least one concordant mutation (44% concordance at the gene level). The concordance rate between ctDNA-mutation/immunohistochemistry-profile was 64% (7/11) for TP53/p53+ and 14% (1/7) for RB1/pRb-. In this pilot study including few patients by subgroups, patients with KRAS (HR=3.60, 95%CI [1.06-12.04]) and BRAF (HR=4.25, 95%CI [1.11-16.40]) mutations had shorter progression-free survival (PFS) under platinum-etoposide, while the two patients with RB1 mutations had shorter PFS under FOLFIRI-based chemotherapy. Twenty-eight periods of treatment were assessed: 10 patients had a molecular response (7/10 had a morphological response), which was associated with longer PFS (HR=0.37, 95%CI [0.15; 0.91]). Conclusion: This pilot study shows a high sensitivity of ctDNA assessment, which is encouraging for the future management of GEPNEC (tumour molecular diagnosis and evaluation of disease progression).

Loyalty is more complex than commonly assumed and involves dimensions of trust, listening, quality of care, availability, and familiarity. The observations drawn out from this study warrant a larger scale investigation.