Wieruszewski, Patrick M.

Abstract Rationale Extracorporeal membrane oxygenation (ECMO) is an increasingly utilized form of life support for patients with cardiac and/or respiratory failure. Fungal infections remain a serious challenge in patients supported by ECMO, with an estimated prevalence of up to 10% and high morbidity and mortality. While routine antifungal prophylaxis is uncommon in ECMO centers and widely debated, its impact on incidence, pathogenic organisms, resistance patterns, and outcomes has not been described. Methods This was a ten-year experience study of fungemia in patients receiving ECMO where most patients received antifungal prophylaxis. Institutional protocol was to prescribe prophylactic fluconazole based on risk stratification, substituted with echinocandins if indicated. Adults (18 years and older) with ECMO runs between 2014-2024 were screened for fungal organism growth on culture, then narrowed to those with positive blood cultures drawn in the window from 24 hours after cannulation through 72 hours after decannulation. Clinical, microbiological, and outcomes data were descriptively summarized. Institutional review board approved with a waiver of informed consent. Results Among 1,039 adult ECMO runs (979 patients), thirteen patients with fungemia were identified for a calculated incidence rate of 1.29 per 1000 ECMO days (95% CI 0.75 to 2.23). Twelve patients (92%) received antifungal prophylaxis; 85% had echinocandin and 38% azole exposure, with some overlap. Median duration of antifungal exposure was 14 days prior to positive culture. Seven patients (54%) had an open sternum at the time of ECMO cannulation, while 11 (85%) had femoral ECMO access. Four patients (31%) had Candida species isolated from other sources prior to fungemia (mediastinum and respiratory system). Candida parapsilosis (31%), C. albicans (23%), and C. guilliermondii (15%) were the most common isolates. The most likely sources were vascular access catheters (38%) and mediastinum (31%). Seven patients (54%) had suspected or confirmed seeding of ECMO hardware after positive blood cultures, though only two circuit exchanges were performed. Four patients (31%) showed evidence of non-susceptibility to their prophylactic antifungal class (Table 1), with a median 35-day exposure prior to positivity among those patients. Only 62% of patients demonstrated blood culture clearance (median 3 [IQR 2.5-7.75] days). Nearly all patients (92%) died within the hospital stay, including all patients with resistant organisms. Conclusions In an ECMO center with routine antifungal prophylaxis practices, the rate of fungemia identified during ECMO support was low. When fungemia developed, there was a high proportion of drug resistance and mortality. This abstract is funded by: None

ABSTRACT Sodium glucose co‐transporter 2 inhibitors (SGLT2i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are nephroprotective and their use is recommended for adults with chronic kidney disease (CKD). The role of SGLT2i and GLP‐1 RAs in patients with acute kidney injury (AKI) is unknown. This systematic review aimed to estimate the effect of SGLT2i or GLP‐1 RAs on clinical outcomes in AKI. We systematically searched Embase, MEDLINE, Scopus, Web of Science Core Collection, and clinical trials registries for observational studies and clinical trials from database inception to July 3, 2025. Included studies evaluated adults (≥ 18 years) with AKI during a hospitalization and compared patients subsequently exposed to either SGLT2i or GLP‐1 RAs to a non‐exposed control group. Random effects meta‐analyses were performed. Six studies related to SGLT2i (five observational, one randomized trial) and one related to GLP‐1 RAs (one observational) met eligibility criteria ( N = 432,048 patients). SGLT2i/GLP‐1 RA exposure was associated with lower odds of major adverse kidney events (MAKE) (OR 0.63, 95% CI 0.46–0.86) and all‐cause mortality [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.21–0.62] compared to controls. The odds for kidney replacement therapy were lower with SGLT2i therapy in the three studies where it was evaluated (OR 0.61, 95% CI 0.40–0.93). Sensitivity analyses restricted to SGLT2i data were consistent with the overall findings [MAKE OR 0.63 (95% CI 0.42–0.95); Mortality OR 0.34 (95% CI 0.18, 0.65)]. Exposure to SGLT2i or GLP‐1 RAs after AKI, examined primarily in observational studies, was associated with improved clinical outcomes. These findings are promising and warrant evaluation in randomized clinical trials.

OBJECTIVE: A definition of refractory septic shock is necessary to guide diagnosis, management, prognostication, research, and future guidelines for this most severe form of the disease. We sought to achieve consensus on clinical criteria that would be used to define refractory septic shock. DESIGN: Review of literature, expert panel position statements, and Delphi rounds with an international expert group. SETTING: Consensus was defined as having at least 75% of panellists in agreement or disagreement on the three highest or lowest levels of a 7-point Likert scale or based on responses to single- or multiple-choice questions, respectively. SUBJECTS: A panel of multinational, multiprofessional and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine (57 invitations and 56 participants). MEASUREMENTS AND MAIN RESULTS: A five-round Delphi process was conducted for consensus and stability. The steering committee proposed 34 statements, and five of them were rejected by panel experts after round 2. Among 29 statements selected from eight domains, consensus was reached for 13. The panel agreed on the need for a comprehensive consensus set of clinical criteria for refractory septic shock. Markers of organ dysfunction (75%, 2 rounds), tissue perfusion (91.1%, 2 rounds) including lactate (94.6%, 2 rounds) and capillary refill time (76.8%, 2 rounds), assessment of fluid-responsiveness after initial resuscitation (92.9%, 5 rounds), and use of vasoactive drugs at norepinephrine equivalents greater than 0.5 µg/kg/min (75.0%, 3 rounds), were selected as clinical criteria of refractory septic shock. The use of critical care ultrasound (CCUS) (92.9%, 3 rounds) was the single diagnostic modality that reached a consensus-based agreement. CONCLUSIONS: A consensus for 13 criteria to frame the definition of refractory septic shock was reached. Refractory septic shock is characterised by persistently elevated lactate concentrations and or prolonged capillary refill time in patients with septic shock who are fluid unresponsive, require a norepinephrine base equivalent dose greater than 0.5 micrograms per kilogram per minute, and undergo CCUS assessment when mixed shock is suspected.