Citations

PURPOSE Remote symptom monitoring using patient-reported outcomes (PROs) has been shown to improve symptom control and physical function among patients with advanced cancer. However, it is unclear whether these benefits are similar across demographic groups. This exploratory analysis of the PRO-TECT trial examined whether the effects of electronic symptom monitoring varied by race, age, sex, and educational attainment. METHODS PRO-TECT was a cluster randomized trial conducted across 52 US community oncology practices comparing weekly electronic symptom monitoring with usual care (UC). Adult patients with metastatic solid tumors receiving systemic therapy were enrolled (N = 1,191). Participants in the PRO arm completed weekly symptom surveys including the PRO-CTCAE, triggering alerts to the care team for severe or worsening symptoms. Patients chose whether to complete weekly PROs online or via telephone-based interactive voice response not requiring Internet access. Outcomes were measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 symptom control and physical function scales. Subgroup analyses were performed by race (Black v White), age (<65 v ≥65 years), sex (male v female), and educational attainment (≤high school v >high school). RESULTS From baseline to 3 months, PRO participants showed greater improvements in symptom control (+2.37 v −0.20, P = .002) and physical function (+1.54 v −0.93, P = .02) versus UC. Benefits were most pronounced among younger, female, Black, and less educated participants. Black participants in the PRO arm were more likely to report that symptom reporting made them feel more in control of their care compared with White participants. CONCLUSION Electronic symptom monitoring improved quality-of-life outcomes overall, including among groups who have historically experienced higher symptom burden or barriers to communication. Remote PRO systems may represent an equitable strategy to enhance cancer care delivery.

Background Pancreatic ductal adenocarcinoma (PDAC), the most common malignant type of pancreatic cancer, is characterized by a dense desmoplastic stroma, low neoantigen burden, and a highly immunosuppressive tumor microenvironment (TME). Methods We present a novel strategy harnessing acute transplant rejection mechanisms by employing a recombinant oncolytic rVMG vector engineered to express murine alloantigens H-2Kb (rVMG-H-2Kb) or H-2Kk (rVMG-H-2Kk), thereby inducing tumor-specific antigenic mismatch responses. Results In vitro, rVMG-H-2Kb and rVMG-H-2Kk exhibited strong replication and cytolytic activity while inducing cell surface expression of both H-2Kk and endogenous H-2Kb, in addition to upregulation of antigen presentation genes (β2-microglobulin, Tap1, and Tapbp). In two immunocompetent PDAC models, intratumoral and systemic delivery of rVMG-H-2Kb and rVMG-H-2Kk delayed tumor progression, with rVMG-H-2Kk conferring a survival advantage. Multiplex immunohistochemistry and immunophenotyping revealed substantial TME remodeling, marked by increased effector T-cell infiltration, regulatory T-cell depletion, and reduced fibrosis. Spatial transcriptomics further showed compartment-specific immune activation and epithelial metabolic reprogramming, corroborating with enhanced tumor immunogenicity. Despite these effects, rVMG-H-2Kk also induced compensatory immunosuppressive pathways, including upregulation of antiviral response genes and immune checkpoint receptors such as programmed death-ligand-2. Importantly, combination therapy with rVMG-H-2Kk and murine checkpoint blockade (anti-programmed cell death protein-1 and anti-cytotoxic T-lymphocyte-associated protein 4) drastically improved survival compared to checkpoint blockade alone. Strikingly, surviving mice resisted tumor rechallenge, indicating the establishment of durable antitumor memory. Conclusion These findings establish rVMG-mediated alloantigen delivery as a novel immunotherapeutic platform capable of converting immune-cold tumors into immune-hot, sensitizing tumors to immune checkpoint inhibitors, and establishing durable antitumor immunity in PDAC.

In participants with Crohn disease (CD), an abbreviated MR enterography (MRE) protocol demonstrated similar interreader agreement to contrast-enhanced MRE and high intrareader concordance for detecting active CD and related complications.

ABSTRACT Attending conferences is a foundational component of professional growth in transplant infectious diseases (TIDs), yet trainees and early‐career faculty often face an overwhelming array of meeting options and limited guidance on how to maximize the experience. This report outlines practical strategies for selecting the most impactful conferences, preparing effectively, engaging with poster sessions, cultivating meaningful professional connections, and incorporating rest and reflection into conference travel. Unlike previous discussions hosted by the TID Early Career Network (TxIDECN), which typically occurred over social media, this was a live expert panel with audience participation at the 2025 Fred Hutch Symposium on Infectious Diseases in the Immunocompromised Host on May 13, 2025, in Seattle, Washington. Here, we summarize that discussion with actionable tools to navigate conferences intentionally and translate these experiences into sustained academic and career development for emerging TID professionals. image

ABSTRACT Observational studies comparing Impella and venoarterial extracorporeal membrane oxygenation (VA‐ECMO) in cardiogenic shock have reported inconsistent findings. We performed an updated systematic review and meta‐analysis, with exploratory matched‐cohort analyses where directly reportable propensity score–matched event‐level data were available. We searched PubMed, Scopus, Web of Science, and the Cochrane Library from inception through March 2026 for observational studies comparing Impella versus VA‐ECMO in adult patients with cardiogenic shock. The primary outcome was in‐hospital mortality. Secondary outcomes included all‐cause mortality, ICU outcomes, access site bleeding requiring transfusion, peripheral vascular complications, renal outcomes, and stroke. Random‐effects models using restricted maximum likelihood were applied. Fifteen observational studies including 22,618 patients were analyzed. In the primary crude analysis, Impella was not associated with a statistically significant difference in in‐hospital mortality (RR 0.84, 95% CI 0.66−1.07; p = 0.15) with substantial heterogeneity ( I ² = 92.9%). However, leave‐one‐out analysis identified an influential registry study; its exclusion markedly reduced heterogeneity and favored Impella ( p < 0.01). In exploratory propensity score‐matched analysis, Impella was also associated with lower in‐hospital mortality (RR 0.69, 95% CI 0.56−0.85, p < 0.01). Thirty‐day and 6‐month all‐cause mortality were neutral, whereas 12‐month mortality modestly favored Impella ( p = 0.048). Sensitivity analyses similarly resolved heterogeneity and favored Impella for selected secondary outcomes, including 6‐month mortality, acute kidney injury, and ischemic stroke. ICU mortality was neutral, while ICU length of stay was shorter with Impella ( p = 0.01). Impella was also associated with lower access site bleeding requiring transfusion ( p < 0.01), peripheral vascular complications ( p < 0.01), and hemorrhagic stroke ( p < 0.01). In this updated meta‐analysis of observational studies, the primary crude analysis of in‐hospital mortality was neutral overall but highly heterogeneous, whereas sensitivity and exploratory matched‐cohort analyses showed a more consistent association favoring Impella. Impella was also associated with lower bleeding and vascular complications and shorter ICU length of stay, although several outcomes remained sensitive to study‐level influence. These findings should be interpreted cautiously given the observational design, predominance of serious risk of bias, and strong potential for confounding by indication.

Abstract Background The Global Bipolar Cohort (GBC) was established to identify existing bipolar disorder (BD) cohorts worldwide and foster collaborations focused on descriptive and analytic outcomes relevant to BD. A distributed analytic framework has been implemented to engage multiple sites without the need for central data pooling. This report describes the GBC endeavor and global functional impairment patterns. Cross-cohort comparisons of functional correlates are limited by heterogeneous measures and data-sharing constraints. Large, culturally diverse comparisons are needed to distinguish broadly reproducible correlates from cohort-specific effects. Participating sites completed a 28-item descriptive survey covering diagnostic methods, cognition, genetics, treatment, functioning, and follow-up strategies. We implemented a harmonized local logistic regression model of dichotomized functional outcome and shared summary statistics only. Results We identified 69 cohorts across five continents. Thirty-seven cohorts contributed functional outcome analyses from 17,130 participants. Outcome measures included clinician-rated disability scales and social indicators such as employment and marital status. The proportion classified with poor functioning ranged from 16% to 77% (mean 50%). In 32 of 37 cohorts, the overall regression model significantly explained variance in functioning. Current depressive symptoms were the most robust and reproducible correlate of poor functional outcome: they were assessed in 29 cohorts, significant in 22 (75.8%), ranked among the top three correlates in 22, and were the top-ranked correlates in 19. Associations between depressive burden and poor functioning were observed across clinician-rated disability scales and work or social indicators, and across geographically diverse cohorts. Comorbid substance use disorder and medication-related variables were associated with poorer functioning in subsets of cohorts, whereas sex, ancestry, bipolar subtype, psychosis history, and premorbid IQ showed weak or inconsistent associations. Cognitive measures, available in a minority of regression models, showed modest and non-uniform effects. Conclusions Across heterogeneous international cohorts, current depressive symptom burden emerged as the most consistent correlate of poor functioning in bipolar disorder. These findings replicate earlier multisite work at a larger scale, show that protocol-based distributed analyses can identify reproducible clinical signals without sharing individual-level data, and support prioritizing detection and treatment of depressive symptoms when aiming to improve real-world functioning. Future work should expand longitudinal harmonization and representation of under-studied populations.

Abstract Aims Alcohol and its relationship with cardiovascular disease (CVD) remain contentious. Several observational studies have found cardioprotective associations, while Mendelian randomization studies have found null or harmful effects of moderate drinking. Biases, including abstainer misclassification and sick-quitter effects, may obscure true associations. It is widely understood that former drinkers are often sick quitters. However, removal of former drinkers from analyses addresses bias in the abstainer group but fails to account for induced survivorship among current drinkers. This study sought to determine whether adjusting for biases altered the association between alcohol and CVD by comparing conventional models with those using (i) occasional drinkers as the reference group instead of lifetime abstainers and (ii) ‘intention-to-treat’ reallocation of former drinkers based on past drinking patterns. Methods and results The Multi-Ethnic Study of Atherosclerosis is a prospective cohort study of 6814 participants aged 45–84 years between 2000 and 2002 without baseline CVD. A total of 6755 participants were included after excluding those with missing data. Alcohol consumption was self-reported and classified as lifetime abstainer, former, or current drinker [occasional (≤1 drink/week), light (2–7 drinks/week), moderate (8–14 drinks/week), heavy (&gt;14 drinks/week)]. Outcomes included coronary artery calcium (CAC; 0, 1–100, 101–300, and &gt;300) and clinical events [myocardial infarction (MI), stroke, cardiovascular mortality, composite major adverse cardiovascular events (MACEs), and heart failure]. Of 6755 participants, 20.6% were lifetime abstainers, 24.1% former drinkers, and 55.3% current drinkers. Adjusting for biases altered the observed relationship between alcohol and CVD, showing increased harm with light drinking, decreased protection with moderate drinking, and a dose–response relationship between alcohol and CAC, particularly CAC &gt;300 in adjusted models. Protective associations between moderate drinking and MI [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.38–1.06] and cardiovascular mortality (HR: 0.81, 95% CI: 0.53–1.25) were attenuated and became non-significant. Light drinking shifted from null to increased risk for MI (HR: 1.46, 95% CI: 1.11–1.92), stroke (HR: 1.54, 95% CI: 1.17–2.03), MACE (HR: 1.33, 95% CI: 1.12–1.57), and heart failure (HR: 1.42, 95% CI: 1.10–1.84). Conclusion Associations between alcohol and CVD in observational studies are sensitive to methodologic variation. Results from models correcting for abstainer/sick-quitter biases may help explain discrepant results from previous studies.

Abstract Introduction Narcolepsy type 2 (NT2) is characterized by excessive daytime sleepiness, heterogeneous symptom severity, and typically normal endogenous orexin levels. The Vibrance-2 phase 2 study evaluated alixorexton, a selective orexin 2 receptor agonist, in patients with NT2. Methods Vibrance-2 was a placebo-controlled, dose-ranging phase 2 study. After a 2-week washout from current narcolepsy medications, adults with NT2 meeting ICSD-3-TR diagnostic criteria were randomized 1:1:1:1 to receive placebo or alixorexton once daily at doses of 10, 14, or 18mg for 8 weeks, followed by an optional 5-week open-label extension. Dual primary endpoints were the change from baseline to week 8 in mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT) and on the Epworth Sleepiness Scale (ESS). Safety evaluation included treatment-emergent adverse events (TEAEs). P-values were adjusted for multiplicity. Results Ninety-three patients were randomized to placebo (n=24) or alixorexton (10mg, n=23; 14mg, n=22; 18mg, n=24); 90 completed double-blind treatment. At baseline, patients had severe symptoms (MWT: 5.6 minutes; ESS: 17.4). The study met its dual primary endpoints. At week 8, MSL on MWT increased 9.3, 6.7, and 6.7 minutes at 10, 14, and 18mg, respectively, from baseline versus placebo, with statistically significant differences observed for the 14 and 18mg doses (adjusted p&lt; 0.05). ESS improved by -2.1, -3.2, and -3.6 points from baseline versus placebo at week 8 for the 10, 14, and 18mg groups, respectively, with statistical significance observed for the 18mg dose (adjusted p&lt; 0.05), where more than 70% of patients achieved normalization. TEAEs in 10% of all alixorexton-treated patients through week 8 were pollakiuria, insomnia, micturition urgency, dizziness, and headache. Most TEAEs were mild-to-moderate with no serious TEAEs. Conclusion Vibrance-2 was the first large clinical trial in patients with NT2 to demonstrate positive results with an orexin 2 receptor agonist. Alixorexton resulted in statistically significant and clinically meaningful improvements in wakefulness and daytime sleepiness at Week 8 and was generally well tolerated. These results support phase 3 clinical development of alixorexton as a treatment for NT2. Support (if any) Alkermes, Inc.

Abstract Introduction Once-nightly sodium oxybate (ON-SXB) is approved to treat cataplexy or excessive daytime sleepiness (EDS) in patients ≥7 years of age with narcolepsy. ON-SXB demonstrated significant improvements in both objective (Maintenance of Wakefulness Test) and subjective (Epworth Sleepiness Scale [ESS] score) measurements of sleepiness in the REST-ON trial and via the ESS in the real-world REFRESH study. Assessing ON-SXB ESS data from a specialty pharmacy and outside of clinical studies further informs the generalizability of effectiveness. Methods Demographic and clinical data were collected from Optum Frontier Therapies pharmacy for patients with ≥1 filled ON-SXB prescription, ≥1 ON-SXB-related clinical assessment, and ≥1 follow-up ESS score (6/1/2023-9/30/2024). Participation in ESS assessment was voluntary. ESS scores were assessed for patients who switched from twice-nightly oxybate (TN-OXB) treatment (first ON-SXB prescription filled ≤30 days of last TN-OXB prescription [switch]) and those new to oxybate or with &gt;30 days between TN-OXB and ON-SXB prescription fills (not-on-oxybate) who had ESS data at initial ON-SXB prescription and at each follow-up assessment. Results Of 452 identified patients, 215 had ≥1 follow-up ESS score (switch, n=82 [mean age, 38.4 years; female, 71%]; not-on-oxybate, n=133 [mean age, 40.0 years; female, 71%]). Of patients who had any prior oxybate use (switch, 100%; not-on-oxybate, 46%), the most common prior oxybate was mixed-salt oxybates (switch, 59%; not-on-oxybate, 70%). Stimulants/wake-promoting agents were taken by 51% of switch and 65% of not-on-oxybate patients. Baseline mean (SD) ESS scores were 11.3 (5.5) for switch and 12.5 (5.6) for not-on-oxybate patients; 23% of switch and 38% of not-on-oxybate patients experienced severe EDS. By the first follow-up (median [IQR], 49 [28-94] days), mean (SD) ESS scores were within the normal EDS range with ON-SXB for both subgroups (ie, ESS &lt; 10; switch, 9.7 [5.5]; not-on-oxybate, 9.5 [5.2]); the majority reported normal levels of daytime sleepiness (switch, 56%; not-on-oxybate, 57%). Mean (SD) change in ESS score from baseline to follow-up was -1.6 [4.5] for switch and -3.1 [5.0] for not-on-oxybate groups. Conclusion Patients who initiated ON-SXB experienced improvements in daytime sleepiness regardless of prior TN-OXB use, and many achieved normal levels of daytime sleepiness in ≤2 months of starting ON-SXB. Support (if any) Avadel Pharmaceuticals