The Efficacy of a Mix of Probiotics (Limosilactobacillus reuteri LMG P-27481 and Lacticaseibacillus rhamnosus GG ATCC 53103) in Preventing Antibiotic-Associated Diarrhea and Clostridium difficile Infection in Hospitalized Patients: Single-Center, Open-Label, Randomized Trial.

BACKGROUND: Antibiotic-associated diarrhea is a condition reported in 5-35% of patients treated with antibiotics, especially in older patients with comorbidities. In most cases, antibiotic-associated diarrhea is not associated with serious complications, but it can prolong hospitalization and provoke Clostridium difficile infection. An important role in the prevention of antibiotic-associated diarrhea is carried out by some probiotic strains such as Lactobacillus GG or the yeast Saccharomyces boulardii that showed good efficacy and a significant reduction in antibiotic-associated diarrhea. Similarly, the Limosilactobacillus reuteri DSM 17938 showed significant benefits in acute diarrhea, reducing its duration and abdominal pain. AIM: The aim of this study was to test the efficacy of a mix of two probiotic strains (Limosilactobacillus reuteri LMG P-27481 and Lacticaseibacillus rhamnosus GG ATCC 53103; Reuterin GG®, NOOS, Italy), in association with antibiotics (compared to antibiotics used alone), in reducing antibiotic-associated diarrhea, clostridium difficile infection, and other gastrointestinal symptoms in adult hospitalized patients. PATIENTS AND METHODS: We enrolled 113 (49M/64F, mean age 69.58 ± 21.28 years) adult patients treated with antibiotics who were hospitalized at the Internal Medicine Department of the San Carlo di Nancy Hospital in Rome from January 2023 to September 2023. Patients were randomized to receive probiotics 1.4 g twice/day in addition with antibiotics (Reuterin GG® group, total: 56 patients, 37F/19M, 67.16 ± 20.5 years old) or antibiotics only (control group, total: 57 patients, 27F/30 M, 71 ± 22 years old). RESULTS: Patients treated with Reuterin GG® showed a significant reduction in diarrhea and clostridium difficile infection. In particular, 28% (16/57) of patients in the control group presented with diarrhea during treatment, compared with 11% (6/56) in the probiotic group (p < 0.05). Interestingly, 7/57 (11%) of patients treated only with antibiotics developed clostridium difficile infection compared to 0% in the probiotic group (p < 0.01). Finally, 9% (5/57) of patients in the control group presented with vomiting compared with 2% (1/56) in the probiotic group (p < 0.05). CONCLUSIONS: Our study showed, for the first time, the efficacy of these two specific probiotic strains in preventing antibiotic-associated diarrhea and clostridium difficile infection in adult hospitalized patients treated with antibiotic therapy. This result allows us to hypothesize that the use of specific probiotic strains during antibiotic therapy can prevent dysbiosis and subsequent antibiotic-associated diarrhea and clostridium difficile infection, thus resulting in both patient and economic health care benefits.

Prognostic role of hypothyroidism and low free-triiodothyronine levels in patients hospitalized with acute heart failure.

Low thyroid function has been widely recognized as a potential cause of heart failure (HF), but the evidence about a possible association with in-hospital, all-cause mortality in patients with acute HF (AHF) is not consistent. This study sought to investigate the prevalence and prognostic role of hypothyroidism, overt and subclinical, and of low free-triiodothyronine (fT3) levels in patients hospitalized with AHF. We retrospectively analyzed consecutive 1018 patients who were hospitalized for AHF in a single academic medical center [Fondazione Policlinico A.Gemelli IRCCS, Rome, Italy] between January 1st 2016, and December 31st 2018. Patients were divided into three groups: normal thyroid function (n = 798), subclinical hypothyroidism (n = 105), and overt hypothyroidism (n = 115). The outcome was in-hospital, all-cause mortality. Patients were 81 years of age, 55% were females and nearly two-thirds of the patients were on New York Heart Association functional class III. The three most common cardiovascular comorbidities were coronary artery disease, hypertension, and atrial fibrillation with no differences across the three groups. Overall, 138 patients (14%) died during the hospital stay. The mortality rate was 27% among patients with overt hypothyroid, 17% among those with subclinical hypothyroidism, and 11% among euthyroid patients (p < 0.001). At a multivariate Cox regression model, overt hypothyroidism (HR 2.1, 95% CI 1.4-3.2) and fT3 levels < 1.8 pg/mL (HR 3.4, 95% CI 2.3-5.1) were associated with an increased likelihood of in-hospital death. No association was found with subclinical hypothyroidism. Among patients hospitalized with AHF, overt hypothyroidism and low fT3 levels are independent predictors of all-cause mortality during the hospital stay.

Enterolactone in breast cyst fluid: correlation with EGF and breast cancer risk.

The purpose of our study was to investigate whether enterolactone does accumulate into breast cyst fluid and whether it correlates with breast cancer risk. We included 258 women who had at least one cyst aspiration and known intracystic cation and epidermal growth factor (EGF) concentration values. For 191 of such women serum aliquots were also available. The median value of serum enterolactone was 17 nM/l (range 1-140 nM/l). The median intracystic level of enterolactone was much higher (63 nM/l, range 0-872 nM/l) and was significantly higher in type I cysts (p = 0.000). This cyst type contained also significantly higher levels of EGF (p = 0.000). A direct relationship was found between serum and cyst fluid enterolactone levels (p = 0.000) and between cyst enterolactone and EGF levels (p = 0.03), the latter correlation being evident especially in type II cysts. Twelve patients in the cohort of women were found to have developed a breast cancer. After univariate analysis breast cancer risk was associated with cyst type and especially with EGF concentration. No association was evident for enterolactone concentration. However, enterolactone concentration appeared to significantly decrease the risk of patients with high EGF concentrations. Our results show that enterolactone does accumulate in breast cysts, and that it modulates the risk related to the intracystic level of EGF, which is confirmed to be a strong predictor of breast cancer risk.