Schulte, Phillip J.

Obesity is common among critically ill adults, but its association with outcomes during venovenous extracorporeal membrane oxygenation (VV ECMO) remains controversial. We evaluated associations of body mass index (BMI) with mortality and Extracorporeal Life Support Organization (ELSO)–defined complications in adults supported with VV ECMO. We conducted a retrospective multicenter cohort study of adults receiving VV ECMO at four centers (2017–2025). The primary outcome was in-hospital mortality; secondary outcomes were ELSO-defined complications. Multivariable logistic regression was adjusted for age, sex, and hospital site; BMI was evaluated as continuous, dichotomized (≥30 vs . <30 kg/m 2 ), and World Health Organization (WHO) obesity class exposures, with interaction testing by coronavirus disease 2019 (COVID-19) status. Among 420 patients (median BMI, 31 kg/m 2 ), in-hospital mortality was 62%. Higher BMI was associated with mortality in non–COVID-19 acute respiratory distress syndrome (ARDS; odds ratio [OR] = 1.06 per 1 kg/m 2 , 95% confidence interval [CI] = 1.02–1.10, p = 0.003) but not in COVID-19 ARDS (OR = 1.00, 95% CI = 0.94–1.05); there was insufficient evidence of interaction between BMI and COVID-19 ( p = 0.07). Higher BMI was associated with renal complications in both groups and infectious complications in non–COVID-19 ARDS (OR = 1.05, 95% CI = 1.02–1.09, p = 0.003). No significant BMI × COVID-19 interaction was detected for any outcomes. These findings do not support an obesity survival paradox during VV ECMO.

Purpose Survivors of critical illness often acquire significant physical, cognitive, and psychological burdens following their intensive care unit (ICU) stay, termed “post-intensive care syndrome” (PICS). Screening for PICS is generally not performed outside of research settings largely due to lack of a simple assessment tool and time constraints. Methods This was a prospective cohort study at a single academic medical center in the USA. We included adults (18 years or older) who spent greater than 48 h in any ICU within the medical center. Following transfer out of the ICU and at 3 months, psychological, cognitive, and physical functioning were assessed using the Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised, Montreal Cognitive Assessment-blind, and Barthel Index. We compared these validated questionnaires to a brief, 15-item PICS screening tool (5 questions/domain) that was developed by our multidisciplinary study team and administered to study participants after ICU discharge to general care. The primary objectives of this study were to assess the ability of validated screening tools administered at ICU discharge to predict PICS at 3 months and develop a novel screening tool for identifying patients at risk of PICS. Major Findings 191 participants completed the initial questionnaire, and 109 (56%) completed the 3-month follow-up. PICS tool scores were compared to 3-month follow-up data from validated questionnaires to evaluate predictive performance. Overall, the screening tool weakly-to-moderately correlated with continuous outcomes of the validated measures at 3-month follow-up. When evaluating sensitivity and specificity for individual domains, the screening tool had an area under curve of >0.7 for all three domains, indicating moderate-to-good sensitivity and specificity. Conclusions We developed a brief PICS screening tool that is feasible to use without prior training that modestly predicted the development of PICS following ICU stay.

ABSTRACT Purpose The natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) remains understudied, with limited long‐term data from large cohorts inclusive of both salvage radiotherapy (SRT)‐treated and untreated patients. Herein, we sought to evaluate the outcomes of patients with BCR and the impact of SRT on disease progression. Materials and Methods Patients undergoing RP who developed BCR (PSA ≥ 0.20 ng/mL) were included. Patients with BCR treated with SRT were compared to untreated patients using risk‐set matching with time‐dependent propensity scores. The primary outcome was metastases, analyzed using Kaplan–Meier and Cox models. The number needed to treat (NNT) with SRT to prevent progression was derived at 5 and 15 years. Results Among 6881 patients with BCR, 2109 received SRT. At a median follow‐up of 10.2 years, 1147 patients developed metastases. The median PSA at the time of SRT was 0.50 ng/mL. After 1:1 propensity score matching (2109 patients per cohort), SRT significantly reduced the risk of metastases at 5 (12.7% vs. 19.3%, p < 0.0001) and 15 years (28.6% vs. 31.5%, p < 0.001). On multivariable analysis, SRT independently reduced metastasis risk (HR 0.75, 95% CI 0.63–0.90, p = 0.002), translating to NNT of 23 and 15 at 5 and 15 years, respectively. Interaction analyses between SRT and nodal status ( p = 0.04) showed greater metastasis risk reduction in pN+ (HR 0.41, 95% CI 0.22–0.77, p = 0.005) compared to pN− disease (HR 0.81, 95% CI 0.67–0.97, p = 0.02). Conclusions Most patients with BCR post‐RP do not progress to metastasis. For those who do progress, SRT inarguably improves the oncologic outcomes in the BCR setting. However, careful patient selection and shared decision making should be encouraged in order to limit overtreatment and side effects.

Background: Cardiac rehabilitation (CR) is essential to secondary cardiovascular disease prevention and management of cardiac patients. Despite its proven benefits, CR remains underutilized with enrollment and completion rates ranging from 10-30% in the US. Yet, there is a scarcity of nationally representative data among diverse populations on socioeconomic differences in barriers and beliefs of CR participation and delivery mode preferences. Hypothesis: The perceptions (barriers, beliefs), CR delivery mode preferences, and CR utilization (prior enrollment) varies by socioeconomic status (SES) among CR-eligible individuals. Methods: We conducted an anonymous national electronic survey from March 2023 to January 2024 of individuals self-reporting a prior CR-eligible diagnosis. The 22-item CR Barriers Scale assessed perceived barriers to CR enrollment and participation using a 5-point Likert scale (strongly disagree to strongly agree). A 13-item, validated questionnaire assessed 4 subscales pertaining to patients’ beliefs about CR, each rated on a 5-point Likert scale (strongly disagree to strongly agree): perceived necessity, concerns about exercise, practical barriers and perceived suitability. CR delivery mode preferences were ascertained (eg, virtual, at-home, etc.). Mean barriers and belief scores as well as delivery mode preferences were stratified by SES. Low SES was defined as ≤ high school education, Medicaid insurance, or uninsured. High SES was defined as > high school education and non-Medicaid health insurance. Responses were analyzed using descriptive statistics with R software. Results: A total of 466 participants completed the survey (38.1% women, 30.6% minoritized racial/ethnic group, 29.6% low SES, 95% response rate) ( Table 1 ). The majority indicated prior enrollment in CR (81.5%) with no difference by SES. CR barrier scores did not differ significantly by SES (p=0.331) ( Table 2 ). Beliefs about CR perceived necessity and perceived suitability differed by SES (p<0.001 and p=0.025), but beliefs regarding concerns about exercise and practical barriers did not. The low SES group reported a higher preference for completely at-home CR compared to the high SES group (33.6% vs 7.4%, p<0.001). Conclusion: Our findings suggest that CR beliefs varied by SES while utilization did not. For CR-eligible patients experiencing socioeconomic disadvantage, at-home CR may be a preferred alternative to center-based CR to increase CR participation and adherence.

Background: Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are leading causes of transfusion-related morbidity and mortality. Soluble factors in erythrocyte supernatant may increase risk for these complications. The authors hypothesized that point-of-care allogeneic erythrocyte washing may be an effective intervention to mitigate elevations in soluble factors as well as physiologic responses associated with transfusion-associated respiratory complications in the setting of cardiac surgery. Methods: This is a two-center, nonblinded, randomized clinical trial evaluating point-of-care washed versus standard issue allogeneic erythrocyte transfusions administered during or on the day of cardiac surgery. The primary analysis was performed via modified intention to treat. The primary outcomes assessed were changes in intermediate markers of lung injury as well as cardiopulmonary physiologic responses to erythrocyte transfusion. Secondary outcomes included the duration of intensive care unit and hospital stay, durations of mechanical ventilation and oxygen supplementation, presence of TRALI or TACO, and mortality. Results: Among 154 analyzed patients (81 washed, 73 standard issue), the median age was 66 yr, and 77 (50.0%) were women. The median (interquartile range) number of allogeneic erythrocyte units transfused on the day of surgery was 3.0 (2.0 to 5.0) in the washed erythrocyte group and 3.0 (2.0 to 4.0) in the standard issue group (P = 0.13). No between-group differences were identified in any of the assessed recipient lung injury biomarkers (all P values > adjusted alpha). Durations of intensive care unit stay (median [interquartile range], 3.0 [2.0 to 5.0] vs. 3.0 [2.0 to 4.0] days; P = 0.117) and hospital length of stay (12.0 [9.0 to 17.0] vs. 12.0 [9.0 to 17.0] days; P = 0.801) were similar, as were the number of ventilator-free days at day 28 (27.0 [27.0 to 27.0] vs. 27.0 [26.0 to 27.0]; P = 0.699) and oxygen-free days at day 28 (24.0 [19.0 to 26.0] vs. 24.0 [22.0 to 26.0]; P = 0.400). No significant differences were noted in mortality rate or in incidence rates for TRALI, TACO, and acute kidney injury. Conclusions: Among patients undergoing cardiovascular surgery with high risk of erythrocyte transfusion, point-of-care washing of allogeneic erythrocyte transfusions did not mitigate changes in intermediate markers of lung injury or cardiopulmonary physiologic responses to erythrocyte transfusion and was not associated with improved clinical outcomes.

Importance Anemia is a common complication of surgery and acute illness that is associated with adverse clinical outcomes. The role of anemia prevention and treatment strategies in this setting remains unclear. Objective To evaluate the effect of a multifaceted anemia management bundle vs standard care on posthospitalization hemoglobin recovery and multidimensional functional outcomes in survivors of acute illness. Design, Setting, and Participants This parallel group randomized clinical trial, known as the Practical Anemia Bundle for Sustained Blood Recovery, was conducted at postsurgical and medical intensive care units at a large US medical center. Critically ill patients (aged ≥18 years) with moderate to severe anemia (hemoglobin concentration &amp;lt;10 g/dL) were enrolled between March 2022 and November 2023. Participants were randomly assigned 1:1 to the intervention or standard care group. Intention-to-treat analyses were performed between July 2024 and January 2025. Intervention The intervention bundle was delivered throughout the duration of hospitalization and included optimized phlebotomy practices, clinical decision support, and pharmacological anemia treatment with intravenous iron. Main Outcomes and Measures The primary outcome was the mean difference in hemoglobin concentration at 1 month after hospital discharge. Results A total of 100 patients (median [IQR] age, 68 [61-72] years; 57 men [57.0%]; 65 [65.0%] with postsurgical admission to the intensive care unit) were enrolled during acute illness. Forty-nine patients (49.0%) were assigned to receive the intervention, and 51 (51.0%) were assigned to receive standard care. Hemoglobin concentration at 1 month after discharge was greater in patients receiving the intervention vs standard care (median [IQR], 12.2 [11.8-13.0] g/dL vs 11.5 [10.2-12.6] g/dL; adjusted mean difference, 0.69 [95% CI, 0.13-1.20] g/dL; P = .02). Conclusions and Relevance This randomized clinical trial found that a multifaceted anemia prevention and treatment bundle was feasible, was well tolerated, and improved posthospitalization hemoglobin concentrations up to 3 months in critically ill adults. These findings can inform the design of future trials. Trial Registration ClinicalTrials.gov Identifier: NCT05167734

ABSTRACTBackgroundCommercial biomarkers and multiparametric MRI (mpMRI) have been utilized to triage men with elevated prostate specific antigen (PSA) and determine patients most likely to harbor clinically‐significant prostate cancer (csPCa). We studied combinations of mpMRI, PSA‐based and novel extracellular vesicle (EV)‐based biomarkers to determine the optimal pre‐biopsy testing to predict csPCa at biopsy.MethodsMen presenting with elevated PSA (≥ 2 ng/mL) were prospectively enrolled and all men underwent clinically indicated mpMRI and blinded study blood draws to determine PSA, prostate health index (PHI) scoring, and EV serum levels. MRI‐fusion transperineal prostate biopsy was performed in all patients. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated, and receiver operator characteristic (ROC) curves were constructed. Bootstrapping analysis was performed to provide more accurate assessment of predictive abilities.ResultsUltimately, 175 consecutive men were prospectively enrolled. Median age in the study population was 65 years. Combinations of biomarkers and MRI demonstrated better predictive ability for csPCa on biopsy than individual modalities. Predictive ability was greatest for PHI density (PHID)‐mpMRI with an AUC of 0.86 (95% CI: 0.80–0.92) while combinations of PSA density ‐mpMRI (AUC: 0.81; 95% CI: 0.73–0.89) and STEAP1‐mpMRI (AUC: 0.77; 95% CI: 0.70–0.86) demonstrated similar ability to predict csPCa. The study is limited by small, predominantly white patient cohort and requires external validation.ConclusionsInclusion of prostate density with biomarkers increases prognostic ability for detecting csPCa. EV density can refine prediction of csPCa and in combination with PHID‐mpMRI leads to superior specificity, thereby decreasing unnecessary biopsies.