BACKGROUND:Posaconazole immediate release (IR) suspension is the standard product for enteral feeding tube (EFT) administration but has erratic pharmacokinetic behaviour, often resulting in subtherapeutic concentrations. Limited evidence suggests that posaconazole oral delayed-release (DR) tablets may be crushed. METHODS:This was a retrospective cohort study of hospitalized adults who received EFT administration of posaconazole IR suspension or crushed DR tablets between 2018 and 2024. Patients were eligible if they had at least one serum drug concentration drawn ≥5 days after posaconazole initiation. The primary outcome was attainment of therapeutic drug concentrations. Secondary outcomes included time to therapeutic serum concentration, adverse drug events, and frequency of occluded EFT. RESULTS:Of the included patients, 48 received IR suspension and 100 received DR tablets. Baseline characteristics and severity of illnesses were well balanced. Among IR suspension and crushed DR tablet recipients, 39% and 80% achieved therapeutic concentrations, respectively (P = 0.002). After adjusting for age, sex, BMI, drug interactions, posaconazole indication and malabsorptive conditions, crushed DR tablets were significantly more likely than IR suspension to achieve therapeutic posaconazole concentrations within 30 days (HR 5.22, 95% CI 2.35-11.61). Occluded EFTs were more frequent among crushed DR tablet recipients (27% versus 10%, P = 0.022), while no differences were observed in the occurrence of hepatotoxicity or hypokalaemia. CONCLUSIONS:With EFT administration, crushed posaconazole DR tablets were associated with a greater likelihood of achieving therapeutic concentrations compared with IR suspension. The optimal technique for administering crushed DR tablets to prevent EFT complications warrants investigation.

Cardiogenic shock in adults continues to carry a high mortality despite advances in cardiac care, interventions and critical care. A major advancement in cardiogenic shock care came with the advent of temporary mechanical circulatory support including the intra-aortic balloon pump, ventricular assist devices, and venoarterial extracorporeal membrane oxygenation (VA ECMO). VA ECMO is a type of temporary mechanical circulatory support used in selected patients with cardiogenic shock that have failed to be adequately supported by less invasive approaches including vasoactive medications, volume optimization, and other temporary mechanical circulatory support. VA ECMO is resource intensive support strategy that requires expertise and cooperation from multiple specialties. Complications during VA ECMO support are common and include bleeding, acute kidney injury, stroke, mechanical complications during cannulation, hemolysis, and limb ischemia. VA ECMO circuits drain blood from the venous system, oxygenate and remove carbon dioxide, and return it to the arterial system, providing biventricular support. VA ECMO may be deployed peripherally (through femoral or internal jugular veins and returning blood to axillary or femoral arteries), or centrally from the right atrium to the aorta. Vascular access used for peripheral VA ECMO is large and includes arterial cannulas (usually 15 to 19 French), venous cannulas (usually 21 to 25 French), and a distal perfusion catheter (5 to 8 French). VA ECMO causes significant physiologic changes including reduced pulmonary blood flow, an inflammatory response, increases in left ventricular afterload, dual circulation when initiated through most peripheral sites, and coagulopathy. Management considerations for patients supported by VA ECMO are complex for multiple reasons including the differing approaches to the underlying cause of cardiogenic shock (for example, ischemic vs. non ischemic etiologies), patient comorbidities, whether the goal is recovery, heart transplant, or dischargeable ventricular assist device. Weaning from VA ECMO is a complex process with multiple possible approaches, and decannulation is most commonly accomplished through surgical or percutaneous approaches. There is a paucity of literature on VA ECMO and most guidance is based on retrospective data and expert opinion. What follows is an overview of VA ECMO for cardiogenic shock.

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.

Cardiac arrest centers (CACs) provide important critical expertise and advanced resources for select out-of-hospital cardiac arrest patients, and their role within regional systems of care is both intuitive and necessary. However, a universal transport strategy for all cardiac arrest patients to CACs is neither evidence-based nor system-efficient. Out-of-hospital cardiac arrest is a heterogeneous syndrome, and outcomes are driven predominantly by prehospital factors, patient characteristics, and arrest etiology. Existing data suggest that benefits associated with treatment at CACs are concentrated within specific subgroups, while indiscriminate transfer may delay stabilization, increase transport-related risk, preclude candidacy for advanced therapies, exacerbate rural-urban disparities, and strain finite critical care resources. A selective, triage-based approach to regionalization, prioritizing patients most likely to benefit from specialized care at CACs, may better optimize outcomes while preserving system resilience and equitable access to care.

In this retrospective cohort study at a quaternary referral hospital, 829 adult patients supported by extracorporeal membrane oxygenation (ECMO) between January 1, 2014, and October 31, 2024, were screened for ventilator-associated pneumonia (VAP). The incidence of VAP in ECMO-supported patients was 17.7 per 1,000 ECMO days (venoarterial [VA] ECMO, 22.1 per 1,000 ECMO days; venovenous [VV] ECMO, 13.8 per 1,000 ECMO days). Median time from ECMO cannulation to diagnosis of VAP was 4 (interquartile range [IQR], 3-8; range 1-84) days. Gram-negative bacteria comprised most respiratory pathogens. A significant increase in minimum ECMO sweep was noted from 2 days before to 1 day after VAP diagnosis (0.79 L/min increase, p = 0.004). Only 38 of 153 patients (24.8%) met National Healthcare Safety Network (NHSN) VAP definitions. After creating a modified VAP definition, which included an ECMO sweep increase of 0.5 L/min as evidence of worsening respiratory status, 78 (51.0%) met the modified definition. Those who met the modified VAP definition had worse in-hospital (60.3% vs. 28.0%, p < 0.001), 30 day (33.3% vs. 17.3%, p = 0.023), and 90 day (53.8% vs. 25.3%, p < 0.001) mortality compared with those who did not meet the modified VAP definition. The incorporation of ECMO parameters into diagnostic criteria may improve detection sensitivity, but further validation is necessary before implementation.

Postcardiotomy shock (PCS) is a distinct form of cardiogenic shock that occurs after cardiac surgery and necessitates rapid decisions regarding temporary mechanical circulatory support (tMCS), including escalation, device configuration, and weaning. Machine learning (ML) has emerged as a strategy to integrate high-dimensional perioperative data and augment clinical decision-making beyond traditional risk scores. This narrative expert review evaluates ML applications across the PCS continuum, including early risk recognition and phenotyping, tMCS initiation, management and liberation, and prognostication. This study also summarizes key aspects of ML model development, including feature selection, outcome definition, external validation, and clinical implementation. Current evidence is strongest for risk stratification, mortality prediction, and weaning support, particularly in venoarterial extracorporeal membrane oxygenation cohorts. However, most models are retrospective, derived from heterogeneous shock populations, and lack prospective validation in PCS-specific cohorts. Emerging work on automated device titration is promising but remains preclinical. ML should be considered an adjunct to clinician judgment rather than a substitute for it. Future progress will depend on high-quality PCS datasets, prospective validation, seamless workflow integration, and governance frameworks that ensure safe, transparent, and equitable implementation.

Abstract: Extracorporeal membrane oxygenation (ECMO) is increasingly used to support patients with severe cardiac or respiratory failure. Neurological complications occur across ECMO configurations and represent a major contributor to mortality and long-term disability. Major neurological complications include ischemic and hemorrhagic stroke, hypoxic ischemic brain injury, seizures, delirium, spinal cord and peripheral nervous system injury, and brain death. The mechanisms underlying neurological injury during ECMO are multifactorial and are influenced by ECMO configuration, reflecting differences in cerebral perfusion, gas exchange, anticoagulation exposure, and precannulation physiologic insults. This review synthesizes neurological complications associated with ECMO, neurological monitoring, and outcomes.

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.

Cardiogenic shock (CS) remains one of the leading causes of in-hospital mortality, with an estimated 40,000 to 50,000 patients being treated for CS each year. Despite major advances in mechanical circulatory support and pharmacologic therapy, short-term outcomes remain poor, with 30-day mortality ranging from 30% to 60%. There is significant heterogeneity in clinical trial design and data, as well as variability in management strategies for patients with CS. In this review article, we aim to summarize current definitions, staging systems, landmark trials, and evolving guideline recommendations, while highlighting trends in outcomes and ongoing gaps in care for patients with CS.