Citations

Background Native American (NA) patients experience persistent inequities in advance care planning (ACP) and often present to tertiary centers with critical illness; culturally respectful serious-illness communication is therefore essential in emergency and intensive care settings. Intervention We developed and implemented a nursing-led, multidisciplinary educational initiative at a large academic medical center serving patients from >50 tribal nations. Informed by a literature review, local practice needs, and expert input from a Native American Patient Experience Ambassador, we created (1) an “Honoring Your Choices” (HYC) communication card with culturally sensitive prompts for serious illness conversations and (2) a quick reference guide (QRG) outlining key cultural considerations and unit-specific resources. Tools were disseminated to seven intensive care units and the emergency department through nurse leader engagement, unit rounding, and staff education, and the initiative was presented at departmental Grand Rounds/didactics with pre/post surveys to assess impact. Results Twenty-seven pre-session and twenty-four post-session surveys were collected from clinicians and trainees. Prior to the session, >80% of respondents reported being not or only slightly confident discussing end-of-life issues with NA patients/families; post-session surveys demonstrated increased self-reported confidence in recognizing when cultural beliefs may influence care and in conducting end-of-life discussions. Conclusions This initiative demonstrates how culturally congruent approaches to serious illness conversations may support more meaningful engagement with NA patients and families. Our experience suggests that developing and evaluating a brief, point-of-care communication tool like Honoring Your Choices may be accomplished with existing interdisciplinary partnerships, offering a practical model that other institutions can readily mirror.

This Perspective discusses whether secondary genomic findings in the clinical context of diagnostic genomic sequencing tests should be sought and reported.

ABSTRACT Objective To compare outcomes of phenobarbital‐based versus benzodiazepine‐based pathways for alcohol withdrawal syndrome (AWS) in critically ill adults and evaluate whether pathway design and timing of phenobarbital use affect treatment outcomes. Data Sources A librarian‐led search of MEDLINE, Embase, Cochrane Central, CINAHL, Web of Science, Scopus, ClinicalTrials.gov , and the World Health Organization International Clinical Trials Registry Platform was conducted through July 2024, with updates in December 2024, August 2025, and December 2025. Search concepts included phenobarbital, benzodiazepines, and alcohol withdrawal. Study Selection and Data Extraction Comparative studies of adults admitted or transferred to an intensive care unit (ICU) with AWS and treated with phenobarbital‐based versus benzodiazepine‐based pathways were included. Sixteen nonrandomized studies were included in the qualitative synthesis, and 12 treatment‐oriented studies were included in the primary meta‐analysis. Multiple reviewers independently screened studies, extracted data, and assessed risk of bias using Risk Of Bias In Non‐randomized Studies—of Interventions (ROBINS‐I). Data Synthesis Phenobarbital‐based pathways were not associated with significantly different intubation (11 studies; odds ratio (OR), 0.62; 95% confidence interval (CI), 0.20–1.87; I 2 = 73%) or hospital length of stay (five studies; mean differences [MD], −1.75 days; 95% CI, −5.07 to 1.56; I 2 = 63%) compared with benzodiazepine‐based pathways. ICU length of stay was shorter with phenobarbital‐based pathways (eight studies; MD, −0.60 days; 95% CI, −0.79 to −0.41; I 2 = 0%). In exploratory subgroup analyses, front‐loaded, protocolized phenobarbital‐first pathways were associated with lower intubation and shorter hospital length of stay, but certainty of evidence was very low. Relevance to Patient Care and Clinical Practice This review distinguishes phenobarbital‐first, protocolized ICU pathways from adjunctive or mixed phenobarbital strategies, suggesting that implementation design may influence outcomes. Conclusions Although evidence remains very low certainty, these findings suggest that phenobarbital's role in ICU AWS may be pathway dependent. Front‐loaded, protocolized phenobarbital‐first pathways may be associated with favorable outcomes in exploratory analyses, but these findings should be considered hypothesis‐generating and require confirmation in prospective randomized trials. Trial Registration: CRD42024595819

IMPORTANCE: Phenobarbital use in ICU alcohol withdrawal syndrome (AWS) may reflect severe or refractory withdrawal and treatment escalation, making multicenter data important to understand its use within ICU practice and its relationship with clinical outcomes. OBJECTIVES: To evaluate phenobarbital use in real-world ICU AWS as a marker of severe or refractory withdrawal and treatment escalation. We also examined its association with time-to-discharge and safety outcomes compared with nonphenobarbital regimens. DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective cohort study using multiple imputation and propensity score matching. Adults with AWS, defined as Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) score greater than or equal to 10, were included if they received a phenobarbital-based or nonphenobarbital-based regimen in ICUs across a large academic health system from June 30, 2017, to July 1, 2024. Postoperative ICU admissions were excluded. MAIN OUTCOMES AND MEASURES: Primary outcomes were time to ICU and hospital discharge alive from treatment initiation. Safety outcomes were hypotension, new intubation, and aspiration within 48 hours. RESULTS: Of 1216 patients, 345 (28.4%) received phenobarbital. Before matching, phenobarbital-treated patients had higher CIWA-Ar, Acute Physiology and Chronic Health Evaluation III, and pre-ICU benzodiazepine exposure, consistent with more severe or refractory withdrawal. In adjusted time-to-discharge models, phenobarbital use was not significantly associated with time to hospital discharge alive (discharge rate ratio [DRR], 0.91; 95% CI, 0.74–1.12; p = 0.370) or ICU discharge alive (DRR, 0.77; 95% CI, 0.59–1.01; p = 0.057). Hypotension and intubation were similar, and aspiration was less frequent with phenobarbital. CONCLUSIONS: In a contemporary ICU cohort, phenobarbital use reflected treatment escalation in patients with more severe or refractory AWS. After adjustment, time to ICU and hospital discharge alive did not differ significantly, hypotension and intubation were similar, and aspiration was less frequent with phenobarbital. Future studies should define optimal timing, dosing, and patient selection.

ABSTRACT Ileus is a common gastrointestinal complication in critically ill patients, posing a unique management challenge due to its multifactorial etiology and impact on clinical stability. Standard therapeutic approaches often fail in the setting of metabolic derangement and hemodynamic instability. Prucalopride, a selective 5-HT 4 receptor agonist, has demonstrated efficacy in promoting colonic motility; however, its use in severe small bowel and colonic ileus or decompensated liver disease populations remains limited. We report the case of a 28-year-old man with decompensated alcoholic hepatitis who developed severe small bowel and colonic ileus refractory to standard management. Concerns for worsening illness prompted a trial of prucalopride, which was temporally associated with rapid resolution of the ileus and remarkable improvement in radiographic imaging and clinical phenotype. Prucalopride may be a potential therapeutic option for severe small bowel and colonic ileus in critically ill patients. Further studies are warranted to delineate its safety and efficacy.

ABSTRACT Beta‐lactam antibiotics (beta‐lactams) are first‐line treatments for most major infectious syndromes in acutely ill patients, with in vitro activity against common pathogens, demonstrated efficacy in trials, and a perceived low risk of adverse effects. The current dosing approach, informed by population‐level data, tends to be simplistically reduced to a “one size fits all” dosing method which only accounts for body weight (i.e., in pediatrics) and end organ function to estimate drug clearance (e.g., estimated glomerular filtration rate); this approach results in substantial variability in observed serum concentrations in acutely ill patients, which can compromise real‐world effectiveness and safety. Beta‐lactam dose individualization, therefore, defined as a dosing regimen for one patient informed by measured concentrations from that patient, has been recommended in international clinical guidelines. Comprehensive guidance on best practices for beta‐lactam dose individualization is lacking. To address this knowledge gap and develop guidance, a multidisciplinary panel of international experts was assembled from the disciplines of infectious diseases, critical care, pharmacometrics, and laboratory medicine, representing both adults and pediatrics. The panel systematically evaluated the literature, using the GRADE approach where feasible, to address broad thematic questions pertaining to whether beta‐lactam dose individualization should be pursued, for what indications beta‐lactam dose individualization is warranted, and the most critical considerations and best practices for implementation of beta‐lactam individualization. The resultant consensus recommendations will equip healthcare professionals caring for acutely ill patients treated with beta‐lactam therapy with the evidence and tools necessary to guide optimal use of beta‐lactam dose individualization.

By acquiring the first human and equipment radiographs in space, this study demonstrated the feasibility of on-orbit radiography and expanded diagnostic capabilities for crew health and hardware evaluation.

Abstract Rationale Lung-protective ventilation protocols use predicted body weight (PBW) to set tidal volumes. However, biases exist in these formulas, with overestimation of lung capacity in older, shorter, female, and non-White patients—groups that experience higher mortality rates during invasive mechanical ventilation (IMV). This study investigated associations between pre-admission forced vital capacity (FVC), driving pressure, and patient outcomes. Methods This multicenter retrospective study included adults (18-95 years old) with pre-admission spirometry who required IMV between 01/01/2016 and 05/31/2025 across the Mayo Clinic, spanning 11 ICUs within 5 hospitals in 4 states. Patients were stratified by FVC/PBW ratio quartiles. The primary outcome was 28-day mortality. Trends were assessed using linear or logistic regression, with FVC/PBW as a continuous variable. Mediation analysis examined pathways between FVC/PBW and mortality, with driving pressure (cm H2O, standardized) as the mediator, and adjusted for covariates including age, sex, SOFA score, and BMI. Absolute risk differences and number needed to harm (NNH) were estimated for key thresholds (e.g. FVC/PBW ≥45 mL/kg, PFTs within 2 years). Results Among 4,839 patients (38.7% female, mean (±SD) age 64.5±13.5 years), FVC/PBW ratio demonstrated substantial individual variation, with a mean of 48.3 ± 13.4 mL/kg. There was systematic variation by demographics (Figure): females had significantly lower ratios than males (45.4 versus 50.2 mL/kg, P < 0.001), and ratios were lower with older age from 52.5 mL/kg in patients <65 to 43.2 mL/kg in those ≥85 years (P < 0.001 for trend). Patients in the lowest FVC/PBW quartile had higher 28-day mortality compared to the highest quartile (26.0% versus 17.0%, P < 0.001) and higher driving pressures (14.0 versus 10.0 cm H2O, P < 0.001; Figure). In mediation analysis (n = 4,147), driving pressure mediated the relationship between FVC and mortality. Each 1-SD increase in FVC/PBW was associated with 0.364-SD lower driving pressure (P < 0.001) and 2.4% lower mortality. The adjusted indirect effect through driving pressure was significant (ACME -0.024, 95% CI: -0.029 to -0.019), accounting for the mortality effect. Sensitivity analyses across binary thresholds, age quartiles, outlier exclusion, and obstructive pathology confirmed robust mediation. Patients with FVC/PBW <45 mL/kg (N = 1,644; 39.6%) had 28-day mortality of 17.8% versus 13.5% for ≥45 mL/kg (risk difference 4.3%, 95% CI 1.8-6.8%; NNH: 23 patients). Conclusions Pre-admission lung function was strongly associated with mortality in adults receiving IMV through driving pressure-mediated pathways. Driving pressure is a modifiable target, especially in patients with smaller lung capacities at highest risk for ventilator-induced lung injury. Further prospective investigation is needed to confirm these findings. This abstract is funded by: National Heart, Lung, and Blood Institute (NHLBI) of the National Institute of Health (NIH) Grant Number K23HL151671

Abstract Rationale Major advances in precision medicine and immunotherapy have led to improved outcomes for patients with metastatic cancer, but have also introduced new, severe toxicities that can necessitate ICU admission. The overall mortality remains substantial; however, prior studies have often been single centered with small sample sizes. Therefore, we sought to provide an overview of the current literature with pooled estimates of short- and long-term mortality. Methods This study was registered a priori on Open Science Framework (10.17605/OSF.IO/438RY) and conducted per the Cochrane Handbook. A medical librarian searched MEDLINE, Embase, PubMed, Cochrane Central Register for Controlled Trials, supplemented by hand searching. Eligible studies included randomized and observational designs with >10 patients; studies were included if ≥ 70% of participants had metastatic disease when subgroup data were unavailable. The primary outcome was ICU mortality. Other outcomes included hospital, 30-day, 3-month, 6-month, and 12-month mortality. Pooled prevalence and 95% CIs were estimated using a random-effects model with Freeman-Tukey transformation. Risk of bias was assessed using the validated 10-item tool for prevalence studies. Results Of 4752 unique citations, 49 were included (N = 168,209). All studies were rated as having low risk of bias with the main threat to external validity being single-center design. Fourteen studies were multi-centered and 3 were multi-national, with the rest being single center. Across 23 studies (N = 2,918), the ICU mortality was 32% (95% CI: 25-39%; I2 = 89%; Figure 1). Across 5 studies (N = 400) with a focus on lung cancer, there was significantly higher ICU mortality (53% [43-64%]; I2 = 75% versus 26% [20-34%]; I2 = 86%; PQ = <0.01). Among 5 studies (N = 474) focusing on acute respiratory failure (ARF), ICU mortality was numerically higher but not statistically significant (49% [33-66%]; I2 = 91% versus 26% [20-34%]; I2 = 85%; PQ=0.07). Hospital mortality was 50% (44-56%; I2 = 99%; N = 157,682), 30-day mortality was 48% (39-57%; I2 = 84%; N = 1,067), 3-month mortality was 69% (62-74%; I2 = 80%; N = 1,296), 6-month mortality was 70% (59-79%; I2 = 91%; N = 1,310), and 12-month mortality was 84% (71-91%; I2 = 95%; N = 1,446; Figure 1). Conclusions Among critically ill adults with metastatic cancer, about one-third died in the ICU, half survived to hospital discharge, and 12-month mortality was 84%. There was considerable heterogeneity in mortality estimates, with worse outcomes in lung cancer. Given that ICU admission criteria and illness severity may differ, large multi-center studies are needed to clarify temporal trends and identify management strategies to improve outcomes. This abstract is funded by: None