Citations

Abstract Introduction Sedation is routinely administered to facilitate comfort and tolerance of life support for critically ill adults dependent on invasive mechanical ventilation. Isoflurane, a widely used anesthetic during surgery, has properties that may also benefit ICU patients requiring continuous sedation. However, efficacy as a sedative and safety in this population is not well established. Methods We conducted two identically designed multicenter randomized trials, INSPIRE ICU1 and INSPIRE ICU2, at hospitals across the US. Ventilator-dependent adults were randomly assigned in a 1.5:1 ratio to receive either inhaled isoflurane or intravenous propofol as the first-line sedative for up to 48 ± 6 hours, targeting a sedation depth between Richmond agitation-sedation scale (RASS) -1 (drowsy) to -4 (responsive only to physical stimuli). Isoflurane was administered via an anesthetic conserving device (Sedaconda ACD-S). In both arms, opioids were permitted at the lowest dose required to achieve freedom from pain. The primary outcome was the percentage of time at target sedation level, assessed as a noninferiority outcome with pre-specified margin of 15%. Secondary outcomes included opioid exposure, wake-up time after end of treatment, time to extubation, and proportion of time with spontaneous breathing effort. Results A total of 470 combined participants were included in the two trials. In each trial, 142 patients were randomly assigned to isoflurane and 93 to propofol. In INSPIRE ICU1, percentage of time within target sedation depth was 77.1 [53.2, 89.9] % with isoflurane and 80.9 [58.2, 96.4] % with propofol (difference -1.5 [-8.9, >99] %; p < 0.01 for noninferiority). In INSPIRE ICU2, percentage of time within target sedation depth was 72.6 [66.4, 78.9] % with isoflurane and 74.5 [67.5, 81.5] % with propofol (difference -1.9 [-9.4, >99] %; p < 0.01 for noninferiority). In both trials, patients assigned to isoflurane received significantly less opioid, measured as fentanyl equivalents, during the treatment period. In INSPIRE ICU2, participants receiving isoflurane were significantly likelier to exhibit spontaneous breathing efforts, but this finding was not replicated in INSPIRE ICU1. There were no significant differences in time to wake-up or time to extubation between groups in either trial. No episodes of malignant hyperthermia or propofol infusion syndrome were reported. Adverse events were comparable in type and frequency between groups. Conclusions In two US multicenter trials, isoflurane was noninferior to propofol for maintaining target sedation depth in adults undergoing invasive ventilation, and was associated with significantly lower opioid exposure. (NCT05327296, NCT05312385) This abstract is funded by: Sedana Medical

Abstract Rationale Long COVID (LC) has affected approximately 400 million people worldwide, with about 20 million in the US. LC is characterized by a host of new symptoms, including neuropsychiatric disorders including cognitive impairment. Disruption of the gut microbiome has been correlated with symptoms of LC. This study examined whether gut microbiome modulation via intake of probiotic fermented foods mitigated psychiatric and cognitive impairments. Methods This was a pilot trial performed at a single academic medical center that enrolled and randomized patients with LC 1:1 into the treatment vs. control arm. Those enrolled into the treatment arm received teaching on the gut microbiome, its relationship to LC, and were encouraged to eat a diet high in probiotic fermented foods for 12 weeks. Those in the control arm did not receive the teaching and were encouraged to eat their normal diet. Diets were tracked using the Mayo Clinic Diet application on a smart phone at least three days per week, and those in the treatment arm received routine calls to discuss protocol adherence and gather subjective feedback on the trial. Neuropsychiatric questionnaires (HADS, IES-R, EQ-5D-5L, and MoCA Blind) were completed at enrollment and upon completion of the trial. Questionnaire scores were evaluated for changes using a paired t-test, with statistical significance defined as a p-value <0.05. Correlation between the fermented food intake and improvements in questionnaires was completed using the Spearman test. Results 43 patients were enrolled; 18 patients in the treatment arm and 20 patients in the control arm completed the trial. Groups did not differ by age, race, education, or baseline neuropsychiatric testing. There was a significant increase in fermented food intake in the treatment arm over the duration of the study. Those in the treatment arm had improvements in questionnaires related to anxiety, PTSD, and quality of life. Those in the control arm only had improvements in reported overall quality of life. Intra-group changes can be seen in Table 1. Correlations between fermented food intake and change in questionnaire scoring showed numerical but not statistically significant improvements in many of the questionnaires, except for the MOCA questionnaire and EQ-5D-5L Self-Care question. Conclusion Implementing a diet high in fermented foods in patients with LC appears to have some signal for improvement in neuropsychiatric symptoms. Completing a larger trial would help clarify if changes would be statistically significant. This abstract is funded by: Mayo Clinic Critical Care Research Committee

OBJECTIVES We aimed to characterize the frequency of major complications of acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) and adolescents present at 6 months after initial presentation. METHODS The Pediatric Research Immune Network on SARS-CoV-2 and MIS-C (PRISM) study was a prospective cohort at 20 US pediatric academic medical centers. Individuals aged younger than 21 years meeting any of the following were enrolled: SARS-CoV-2 detection within 7 days, Centers for Disease Control and Prevention (CDC) MIS-C criteria, or CDC MIS-C criteria except having involvement of 1 organ system. The study was designed to assess the proportion of children with major complications (cardiovascular, pulmonary, gastrointestinal/hepatic, renal, and/or neurologic) 6 months after presentation. RESULTS Data were analyzed on 229 hospitalized participants: 59 with COVID-19 (mean age 10.4 years; SD, 5.5) and 170 with MIS-C (mean age 10.1 years; SD, 4.8). Overall, 42.8% were female, making up 55.9% and 38.2% of the COVID-19 and MIS-C groups, respectively. Overall, the frequencies of major complications at 6 months after initial presentation were: 16/195 (8.2%) cardiovascular, 11/154 (7.1%) pulmonary, 11/154 (7.1%) gastrointestinal/hepatic, 3/152 (2.0%) renal, and 3/189 (1.6%) neurologic. Organ system complications did not differ significantly between the COVID-19 and MIS-C groups. Six of 14 (42.9%) COVID-19 and 21/26 (80.7%) MIS-C participants with at least 1 six-month complication had no underlying medical condition that may have been associated with their complication(s). CONCLUSIONS Major complications were infrequent but observed in children without underlying medical conditions, underscoring the importance of prospective follow-up to optimize management and elucidate the complications associated with severe SARS-CoV-2 infection in children.

Elevated intratumoral interstitial fluid pressure (IFP) can negatively impact the efficacy of neoadjuvant chemotherapy (NAC) of breast cancer. This study aims to predict breast cancer pathological complete response (pCR) to NAC based on IFP measures by 3-D subharmonic-aided pressure estimation (SHAPE). SHAPE uses the inverse linear relationship between hydrostatic pressure and subharmonic signal magnitude from intravascular ultrasound contrast agents. Thirty-eight breast cancer patients undergoing NAC from three clinical sites were enrolled for this study. SHAPE data were collected for each subject at 0%, 10%, and 30% of NAC completion using a Logiq E9 system (GE HeathCare) equipped with an RSP6-16D probe. The contrast agent used was Definity (Lantheus Medical Imaging). The subharmonic signal gradients between tumor and adjacent normal tissue were calculated and compared with patient pathological response outcome using t-test and receiver operating characteristic (ROC) curve analysis. Pressure gradients between pCR (15 patients) and non-pCR (23 patients) groups were significantly different at 0 (p = 0.02), 10 (p = 0.03), and 30% (p = 0.0003) completion of NAC. Area under the curve values of 0.69, 0.77, and 0.86 were achieved at 0%, 10%, and 30% of NAC completion, respectively. Overall, SHAPE pressure gradients may aid prediction of NAC pathological response in breast cancer patients.

By 2045, more than three quarters of global cancer deaths are projected to occur in low- and middle-income countries (LMICs); however, the global availability of cancer care remains constrained by high costs and inequitable access. Value-based frameworks that integrate clinical benefit with affordability, feasibility, and equity are essential to better guide research prioritization, resource allocation, and regulatory policies in LMICs. A key component of a value-based approach is the generation of high-quality, locally relevant data to support evidence-based implementation of cancer prevention and control strategies. Herein, we provide three contemporary examples from JCO Global Oncology which demonstrate how economic evaluation in cancer research can address locally relevant, health system–specific questions.

Importance Current risk prediction guidelines for hypertrophic cardiomyopathy predict only sudden cardiac death and are imperfect, leading to avoidable deaths and unnecessary implantable cardioverter defibrillators. Objective To combine prospectively collected clinical history, imaging, genetic, and biomarker data to improve risk prediction of adverse events in hypertrophic cardiomyopathy. Design, Setting, and Participants A total of 2750 patients with hypertrophic cardiomyopathy were prospectively enrolled in the registry-based study from 44 sites in North America and Europe with expertise in hypertrophic cardiomyopathy and cardiac magnetic resonance (CMR) imaging. Participants were enrolled from April 1, 2014, to April 7, 2017. Exposures Patients underwent a health history questionnaire, blood sampling for biomarkers and genotyping, and contrast-enhanced CMR. Patients were followed up yearly by telephone and through records review regarding event documentation. Main Outcomes and Measures The predefined composite adjudicated primary end point was time to first event for hypertrophic cardiomyopathy–related deaths; nonfatal sustained ventricular arrhythmias (VAs) requiring cardioversion or defibrillation; and left ventricular (LV) assist device implant or heart transplant. A secondary end point was a composite of sudden cardiac death and nonfatal VA events. The elastic-net method identified the most important predictors. Cox proportional hazards regression assessed associations with time to the first end point. Results Of the 2750 prospectively enrolled patients, 2698 (98%) had analyzable data after 9 were excluded because they had hypertrophic cardiomyopathy phenocopies and 43 withdrew. Of these remaining patients, 1919 (71%) were male, mean age was 50 years (SD, 11 years), and 423 (16%) were from underrepresented racial and minority groups. The mean follow-up was 6.9 years (SD, 2.1 years). The primary event model in 104 patients included LV scar as a percentage of LV mass by late gadolinium enhancement (LGE%; hazard ratio [HR], 1.86; 95% CI, 1.58-2.20; P < .001), LV mass index (HR, 1.09; 95% CI, 1.01-1.17; P = .03), LV end-systolic volume index (HR, 1.28; 95% CI, 1.12-1.46; P < .001 ), all per 10-unit increase, history of heart failure at study entry (HR, 2.89; 95% CI, 1.75-4.77; P < .001), and log N-terminal pro–B-type natriuretic peptide (NT-proBNP; HR, 1.41; 95% CI, 1.17-1.70; P < .001) level per log unit, (C index for all, 0.77). An LGE percentage of the LV mass of 9% or higher substantially increased the primary composite event rate ( P = .001). The secondary sudden cardiac death and VA risk factor model (in 69 patients) included LGE%, LV mass index, LV ejection fraction, and log(NT-proBNP) (C index, 0.76). Conclusions and Relevance These results provide prospective evidence for incorporating cardiac magnetic resonance and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy. Trial Registration ClinicalTrials.gov Identifier: NCT01915615

Abstract Introduction Low-sodium oxybate (LXB; Xywav®), the only FDA-approved treatment for idiopathic hypersomnia in adults, was evaluated in the phase 4, open-label DUET study (NCT05875974). This post-hoc analysis evaluated subgroups of participants with idiopathic hypersomnia stratified by patient-reported ideal nighttime sleep duration (with [>9 hours] and without [≤9 hours] long sleep need [LSN]), based on Idiopathic Hypersomnia Severity Scale (IHSS) Item 1. Methods DUET included screening, 8-day baseline (BL), 2−8-week LXB dose titration/optimization, 2-week stable-dose, 8-day end-of-treatment (EOT), and 2-week safety follow-up periods. Outcomes were Epworth Sleepiness Scale (ESS), IHSS, polysomnographic total sleep time (TST), and Patient Global Impression of Severity (PGI-S) and Change (PGI-C). Least squares mean (LSM) changes (BL-to-EOT) were BL-adjusted; P values are nominal. Treatment-emergent adverse events (TEAEs) were assessed by subgroup. Results Of 46 enrolled participants with idiopathic hypersomnia, 45 had BL IHSS data; 24 reported LSN (>9 hours) and 21 reported no LSN (≤9 hours). Most (LSN/without LSN) were female (100%/61.9%) and White (91.7%/76.2%), with mean±SD age 36.8±11.1/38.6±12.1 years; 20/24 and 19/21 completed the study. BL mean±SE (LSN/without LSN) ESS scores were 16.8±0.5/16.1±0.7; LSM changes (95% CI): LSN −9.5 (−11.5, −7.6; P< 0.0001; n=20), without LSN −7.4 (−9.4, −5.4; P< 0.0001; n=19). BL mean±SE (LSN/without LSN) IHSS total scores were 35.7±1.3/30.5±1.8; LSM changes (95% CI): LSN −18.3 (−22.4, −14.1; P< 0.0001; n=19), without LSN −12.5 (−16.9, −8.0; P< 0.0001; n=17). BL mean±SE (LSN/without LSN) IHSS long sleep/sleep inertia component scores were 12.5±0.6/9.2±0.6; LSM changes (95% CI): LSN −5.5 (−6.8, −4.1; P< 0.0001; n=19), without LSN −4.0 (−5.4, −2.5; P< 0.0001; n=17). BL mean±SE (LSN/without LSN) polysomnographic TSTs were 490.0±26.0/442.7± 24.7 minutes; LSM changes (95% CI): LSN −53.1 (−92.5, −13.7; P=0.0097; n=20), without LSN −59.4 (−99.8, −18.9; P=0.0052; n=19). On the PGI-C, most participants (LSN/without LSN) endorsed improved overall disease (100%/88.2%; n=19/n=17) at EOT. TEAEs were reported in 79.2% (LSN) and 66.7% (without LSN); most (LSN/without LSN) were mild (45.8%/42.9%) or moderate (33.3%/23.8%) in severity; 1 (without LSN) was serious (unrelated to study drug). Conclusion Participants with or without LSN (>9 hours or ≤9 hours, respectively) taking LXB showed improvements in multiple idiopathic hypersomnia symptoms and reduced TST. Support (if any) Jazz Pharmaceuticals

INTRODUCTION: Adverse events (AEs) in health care—such as medical errors and patient harm—are a leading cause of death in the United States and have long-lasting emotional and behavioral effects on patients and families. Effective communication following AEs is critical, yet providers often lack training, institutional guidance, and confidence to navigate these conversations. Communication training programs have shown promise in improving provider empathy, competence, and confidence, but there is limited data on ob-gyn practicing providers, allied health care staff, and administrators. METHODS: A 4-hour multidisciplinary communication training was conducted at a large Midwestern academic hospital system (2022–2024). Training included didactics, simulated patient scenarios, and group debriefings. Participants were ob-gyn clinicians, nurses, and administrative staff. In 2025, 58 participants received follow-up surveys; 33 responded. Quantitative data were analyzed with SPSS, and qualitative responses underwent thematic analysis. RESULTS: Post-training, participants reported high empathy (mean 4.38, SD .38), communication competence (mean 4.45, SD .49), and confidence (mean 4.28, SD .43). No significant differences existed between clinical and nonclinical groups. Qualitative feedback included better empathy, structured conversations, and comfort apologizing. Ninety-seven percent reported changed communication practices, and 91% applied skills in practice. CONCLUSIONS/IMPLICATIONS: Training led to sustained empathy and confidence improvements across roles and specialties. Participants noted high uptake and ongoing use of skills. To our knowledge, there are no other published studies on the effect of communication training in practicing ob-gyn providers, allied staff, and administrators. Future efforts should add unscripted scenarios and behavioral assessments beyond self-report.

PURPOSE Although outcomes for nonmetastatic cancers have improved since the 1970s, it remains uncertain whether long-term survival has improved among patients presenting with de novo metastatic disease, defined as cancer presenting with distant metastases at the time of initial diagnosis. This study evaluated changes in 5-year survival among patients with de novo metastatic cancer diagnosed in 1976 versus 2015, with a minimum 5-year follow-up through 1981 and 2020, respectively. METHODS Population-based data were obtained from the SEER database. Patients diagnosed with de novo metastatic cancer in 1976 (n = 11,864) and 2015 (n = 26,324) were included. Five-year overall survival (OS) was compared between cohorts, and multivariable logistic regression identified demographic and clinical factors associated with survival. RESULTS The 5-year OS increased significantly from 10.6% in 1976-1981 to 23.6% in 2015-2020 ( P < .001). Survival gains were largest in breast cancer (12.6%-34.2%; P < .001), ovarian cancer (14.4%-32.5%; P < .001), colorectal cancer (3.7%-15.0%; P < .001), and hematologic malignancies (24.3%-53.9%; P < .001). Minimal improvement occurred in pancreatic cancer (0.25%-1.6%; P = .007) and small cell lung cancer (0.8%-3.1%; P = .008). Multivariable analysis demonstrated that older age, male sex, and Black race were associated with lower odds of 5-year survival (all P < .01) CONCLUSION Over the past four decades, long-term survival among patients with de novo metastatic cancer has more than doubled; however, progress remains uneven across cancer types. Gains appear concentrated in malignancies with substantial therapeutic advances, whereas others show persistently poor outcomes. Continued efforts are needed to address disparities and improve survival in resistant cancer types.