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Background: No previous study investigated the dexmedetomidine-based opioid-free anesthesia (OFA) protocol in cardiac surgery. The main objective of this study was to evaluate the feasibility and the postoperative opioid-sparing effect of dexmedetomidine-based OFA in adult cardiac surgery patients., Methods: We conducted a single-centre and retrospective study including 80 patients above 18 years old who underwent on-pump cardiac surgery between November 2018 and February 2020. Patients were divided into two groups: OFA (lidocaine, ketamine, dexmedetomidine, MgSO4) or opioid-based anaesthesia (remifentanil and anti-hyperalgesic medications such as ketamine and/or MgSO4 and/or lidocaine at the discretion of the anesthesiologist). The primary endpoint was the total amount of opioid consumed in its equivalent of intravenous morphine during the first 48 postoperative hours. Secondary outcomes included perioperative hemodynamics, post-operative maximal pain at rest and during coughing and adverse outcomes. Data are expressed as median [interquartile range]., Results: Patients in the OFA-group had a higher EuroSCORE II, with more diabetes, more dyslipidemia and more non-elective surgery but fewer smoking history. In the OFA group, the median loading dose of dexmedetomidine was 0.6 [0.4-0.6] μg.kg - 1 while the median maintenance dose was 0.11 μg.kg - 1 .h - 1 [0.05-0.20]. In 10 (25%) patients, dexmedetomidine was discontinued for a drop of mean arterial pressure below 55 mmHg. The median total amount of opioid consumed in its equivalent of intravenous morphine during the first 48 postoperative hours was lower in the OFA group (15.0 mg [8.5-23.5] versus 30.0 mg [17.3-44.3], p < 0.001). While no differences were seen with rest pain (2.0 [0.0-3.0] versus 0.5 [0.0-5.0], p = 0.60), the maximal pain score during coughing was lower in OFA group (3.5 [2.0-5.0] versus 5.5 [3.0-7.0], p = 0.04). In OFA group the incidence of atrial fibrillation (18% versus 40%, p = 0.03) and non-invasive ventilation use (25% versus 48%, p = 0.04) were lower. The incidence of bradycardia and the intraoperative use of norepinephrine were similar between both groups., Conclusion: Dexmedetomidine-based OFA in cardiac surgery patients is feasible and could be associated with a lower postoperative morphine consumption and better postoperative outcomes. Further randomized studies are required to confirm these promising results and determine the optimal associations, dosages, and infusion protocols during cardiac surgery.

Recent developments in the understanding of the relationship between the microbiota and its host have provided evidence regarding the therapeutic potential of selected microorganisms to prevent or treat disease. According to Directive 2001/83/EC, in the European Union (EU), any product intended to prevent or treat disease is defined as a medicinal product and requires a marketing authorization by competent authorities prior to commercialization. Even if the pharmaceutical regulatory framework is harmonized at the EU level, obtaining marketing authorisations for medicinal products remains very challenging for Live Biotherapeutic Products (LBPs). Compared to other medicinal products currently on the market, safety assessment of LBPs represents a real challenge because of their specific characteristics and mode of action. Indeed, LBPs are not intended to reach the systemic circulation targeting distant organs, tissues, or receptors, but rather exert their effect through direct interactions with the complex native microbiota and/or the modulation of complex host-microbiota relation, indirectly leading to distant biological effects within the host. Hence, developers must rely on a thorough risk analysis, and pharmaceutical guidelines for other biological products should be taken into account in order to design relevant non-clinical and clinical development programmes. Here we aim at providing a roadmap for a risk analysis that takes into account the specificities of LBPs. We describe the different risks associated with these products and their interactions with the patient. Then, from that risk assessment, we propose solutions to design non-clinical programmes and First in Human (FIH) early clinical trials appropriate to assess LBP safety., (Copyright © 2020 Rouanet, Bolca, Bru, Claes, Cvejic, Girgis, Harper, Lavergne, Mathys, Pane, Pot, Shortt, Alkema, Bezulowsky, Blanquet-Diot, Chassard, Claus, Hadida, Hemmingsen, Jeune, Lindman, Midzi, Mogna, Movitz, Nasir, Oberreither, Seegers, Sterkman, Valo, Vieville and Cordaillat-Simmons.)

Left ventricular assist devices (LVADs) are used as an alternative therapy for heart transplantation in patients with advanced heart failure. However, the mortality rate of these patients remains relatively high. A large proportion of deaths after LVAD implantation occur during intensive care unit (ICU) stay. We conducted a retrospective study to identify the risk factors for all-cause ICU mortality in patients with an implanted LVAD. Between January 1, 2008 and December 31, 2016, 70 consecutive patients who had received an LVAD were analyzed. The median ICU length of stay was 14 days (IQR: 8-31) and 16 patients (22.9% [95%CI: 13.1-32.7]) died in the ICU. The 90-day mortality rate was 25.7% (95%CI: 15.5-35.9). The main causes of ICU mortality were: multiple organ failure, stroke, and hemorrhagic events. The univariate analysis identified the following perioperative risk factors for all-cause ICU mortality: hypertension, preoperative platelet count, preoperative white cell count, inotropic support before LVAD implantation, mechanical ventilation before LVAD implantation, renal replacement therapy before LVAD implantation, short-term mechanical support before LVAD implantation, INTERMACS class 1 to 2, low intraoperative platelet count, low early postoperative hemoglobin level, low early postoperative platelet count, low early postoperative pH, and massive perioperative blood transfusion. In the multivariate logistic regression analysis, only mechanical ventilation before LVAD implantation was retained as an independent risk factor for ICU mortality (OR = 11.96 [95%CI: 2.67-53.45], P < .01). These findings confirm that most deaths after LVAD implantation occur in the ICU. Patients that receive mechanical ventilation preoperatively have the highest risk of death. This confirms the need to actively treat respiratory failure and to wean patients from respiratory support before LVAD implantation. Such a strategy offers the best opportunity to initiate active rehabilitation., (© 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: A high perioperative blood lactate level has been reported to be associated with poor outcomes after cardiac surgery. More than isolated peaks of lactate values, it should be more interesting to take into account changes in intraoperative blood lactate level (∆Lact). This large-scale retrospective study evaluated the relationship between ∆Lact and overall intensive care unit morbidity and 30-day all-cause mortality., Methods: Perioperative data from consecutive patients undergoing on-pump cardiac surgery between September 2010 and June 2016 were retrospectively analysed through our institutional database including clinical, transfusion and laboratory test results implemented prospectively by physicians. Blood lactate levels were initially measured after induction of anaesthesia (baseline) and periodically during the surgery. The ∆Lact was defined as the difference between the highest intraoperative blood lactate and the baseline lactate level and offered the opportunity to stratify patients into four subgroups: ⩽0, 0.1-0.9, 1-1.9 and ⩾2 mmol L -1 ., Results: From the 7,795 patients found eligible during the study period, 7,447 patients were analysed. The median ∆Lact of our patients was 0.6 (0.3-1) mmol L -1 . Most of the studied patients (65.9%) exhibited a ∆Lact between 0.1 and 0.9 mmol L -1 . A concentration-dependent relationship was observed between ∆Lact and intensive care unit morbidity and 30-day mortality. After adjustment for co-variables, all ∆Lact > 0 was associated with an increase in overall intensive care unit morbidity. An independent relationship was also found between ∆Lact and 30-day mortality as of a 1 mmol L -1 increase., Conclusion: Our results suggest that ∆Lact is associated with poor short-term outcomes in adult cardiac surgical patients.

Background: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain and/or discomfort. Probiotics have been reported to benefit IBS symptoms but the level of benefit remains quite unclear., Objective: This study was designed to assess the benefit of Saccharomyces cerevisiae I-3856 on IBS symptoms., Methods: A randomized, double blind, placebo-controlled trial has been performed in 379 subjects with diagnosed IBS. Subjects were randomly supplemented with the probiotics (1000 mg) or placebo for 12 weeks. Questionnaires (gastrointestinal symptoms, stools, wellbeing, and quality of life) were completed. Primary endpoint was percentage of responders defined as having a 50% decrease in the weekly average "intestinal pain/discomfort score" for at least 4 out of the last 8 weeks of the study., Results: There was no overall benefit of S. cerevisiae I-3856 on IBS symptoms and wellbeing in the study population. Moreover, S. cerevisiae I-3856 was not statistically significant predictor of the responder status of the subjects (p > 0.05). Planned subgroup analyses showed significant effect in the IBS-C subjects: improvement of gastrointestinal symptoms was significantly higher in active group, compared to placebo, on abdominal pain/discomfort and bloating throughout the study and at the end of the supplementation., Conclusions: In this study, S. cerevisiae I-3856 at the dose of 1000 mg per day does not improve intestinal pain and discomfort in general IBS patients. However, it seems to have an effect in the subgroup with constipation which needs further studies to confirm (NCT01613456 in ClinicalTrials.gov registry).

Background: Bacillus probiotics health benefits have been until now quite poorly studied in the elderly population. This study aimed to assess the effects of Bacillus subtilis CU1 consumption on immune stimulation and resistance to common infectious disease (CID) episodes in healthy free-living seniors., Results: One hundred subjects aged 60-74 were included in this randomized, double-blind, placebo-controlled, parallel-arms study. Subjects consumed either the placebo or the probiotic (2.10(9) B. subtilis CU1 spores daily) by short periodical courses of 10 days intermittently, alternating 18-day course of break. This scheme was repeated 4 times during the study. Symptoms of gastrointestinal and upper/lower respiratory tract infections were recorded daily by the subjects throughout the study (4 months). Blood, saliva and stool samples were collected in a predefined subset of the first forty-four subjects enrolled in the study. B. subtilis CU1 supplementation did not statistically significantly decrease the mean number of days of reported CID symptoms over the 4-month of study (probiotic group: 5.1 (7.0) d, placebo group: 6.6 (7.3) d, P = 0.2015). However, in the subset of forty-four randomized subjects providing biological samples, we showed that consumption of B. subtilis CU1 significantly increased fecal and salivary secretory IgA concentrations compared to the placebo. A post-hoc analysis on this subset showed a decreased frequency of respiratory infections in the probiotc group compared to the placebo group., Conclusion: Taken together, our study provides evidence that B. subtilis CU1 supplementation during the winter period may be a safe effective way to stimulate immune responses in elderly subjects.