Citations

Background Compassionate extubations (CEs) can be categorized as stressful clinical events that have potential to trigger a second victim response. The Second Victim Experience and Support Tool-Revised (SVEST-R) is a survey used by healthcare organizations to evaluate second victim experiences of their staff. The purpose of this study was to quantify the level of agreement among respiratory therapists (RTs) who participate in CEs resulting in the perception of being a second victim, as well as various desired forms of support. Methods The study employed a cross-sectional, non-experimental survey design. The SVEST-R was disseminated via an anonymous electronic survey posted to a private social media site for RTs. Data analysis included descriptive statistics for demographic variables, exploratory factor analysis, measures of reliability for the SVEST-R instrument, and comparison of responses across demographic variables. Results There were 146 survey responses. The majority of respondents were female (92%), between the ages of 25–40 (49%), had between 11 and 20 years of RT experience (27%), and practiced primarily in adult critical care (87%). Up to 51.4% of the sample reported that physical distress had occurred due to participation in CEs. The majority of respondents (80.8%) agree that colleague support is present. There was general agreement that supervisor (>60%) and organization (>50%) support are present. Perception of professional self-efficacy was preserved, and resilience remained high for the majority of RTs in this sample. There was general disagreement that involvement in CEs resulted in absenteeism from work or turnover intentions. The most frequently desired form of support was a peaceful location to recover and recompose after the event (85.8%). Conclusions RTs experience marginal yet meaningful distress as a result of participating in CEs. Respondents desire more opportunities to exist in terms of institutional support. Participating in CEs rarely impacts perceptions of self-efficacy. Respondents identify as resilient and feel the experiences with CEs have promoted professional growth.

ABSTRACT Pathogenic variants in MAPK8IP3 (JIP3) cause Neurodevelopmental Disorder with or without variable Brain Abnormalities (NEDBA), characterized by cognitive impairment, global developmental delay, motor dysfunction, abnormal muscle tone, behavioral dysregulation including autism and attention deficit hyperactivity disorder (ADHD), seizures, and structural brain abnormalities. While more than 30 largely de novo MAPK8IP3 variants have been reported, the functional impact of variants across JIP3 protein structural domains is poorly defined. To address this knowledge gap, we compare clinical features of individuals with a truncating (p.E27X) or one of two missense (p.R578C and p.R1146C) variants from distinct JIP3 functional protein domains to corresponding knock-in mouse models. Our findings showed that all individuals, regardless of variant type, exhibited delays in language and gross motor function, but individual variants were associated with distinct motor, cognitive, and psychiatric symptoms. Corresponding homozygous p.E27X and p.R1147C variant mice resulted in embryonic lethality, consistent with essential roles for JIP3 in early neurodevelopment. Behavioral characterization of viable heterozygous mice revealed variant-specific locomotor, motor coordination, and hindlimb clasping defects that closely recapitulate clinical observations. Heterozygous p.R579C mice exhibited reduced locomotion, impaired motor performance, and hypertonia-like clasping, mirroring human motor deficits. In contrast, p.R1147C mice displayed hyperactivity, hindlimb clasping, and decreased brain weight, paralleling human clinical features. Together, our findings demonstrate that while distinct MAPK8IP3 variants lead to some shared phenotypes, they are also associated with distinct phenotypes that could reveal domain-specific aspects of JIP3 function. This work establishes the first domain-resolved in vivo rodent models of NEDBA and provides a validated translational platform for mechanistic investigation and preclinical therapeutic testing.

Myelodysplastic syndromes (MDS), which are hematopoietic stem cell malignancies, are often accompanied by signs of chronic inflammation, that can in turn drive the pathogenetic process. The precise mechanisms dysregulating inflammatory and innate immune signaling in MDS hematopoietic stem and progenitor cells (HSPCs) remain under investigation. We report that mice lacking Tet2 developed a hyper-inflammatory state, which can be further fueled by LPS-induced inflammation. This chronic inflammation temporarily promotes the self-renewal and myeloid differentiation of Tet2-deficient HSPCs; however, it ultimately accelerates HSC exhaustion and triggers MDS development in chimeric mouse models. Driving this phenotype was the activation of the NLRC4 inflammasome pathway. Notably, Nlrc4 depletion in Tet2-deficient mice impaired MDS development and improved the survival of these mice. These findings uncover a novel mechanistic basis for the MDS-associated inflammation and provide new targeting opportunities in its management.

Abstract Black/African American populations, globally, bear the greatest prostate cancer (CaP) burden compared to other racial/ethnic groups. Addressing CaP disparities in Black men is complex, requiring a patient-centered, community-centric and comprehensive approach. This study integrates iCCaRE Consortium findings and broader literature to address unmet needs in survivorship care. The iCCaRE Consortium implemented five complementary pilot studies using mixed-methods designs, including feasibility trials, qualitative research, and observational analyses across the United States and sub-Saharan Africa. Descriptive statistics, subgroup analyses, and qualitative thematic analyses were performed across these studies. Collectively, projects addressed multilevel determinants including social, behavioral, and biological drivers of disparities. Project 1 implemented a Virtual Reality Assistant (ViRA) across clinical and community settings, with ongoing evaluation in pragmatic trials. Project 2 showed strong patient preference for home-based cancer care. Project 3 enrolled demonstrated trends toward improved health-related quality of life. Project 4 identified key themes influencing survivorship experiences. Project 5 identified biological mechanisms linking stress, immune modulation, and symptom burden. The iCCaRE pilot projects demonstrate the feasibility and early impact of a consortium-based, transdisciplinary approach to addressing CaP disparities in Black men. These findings highlight the importance of integrating patient-centered interventions, community engagement, and biological insights to inform scalable strategies aimed at improving survivorship outcomes and advancing health equity. The iCCaRE Consortium demonstrates that a transatlantic, patient-centered, and multidisciplinary approach integrating social, clinical, and biological factors can generate scalable strategies to improve survivorship outcomes and advance equity in CaP care for Black men.

Background Randomized trials have shown equivocal outcomes between a direct aspiration as first-pass technique (ADAPT) and stent retriever (SR) stroke thrombectomy, yet whether specific patient subgroups benefit differentially from one technique over the other remains unknown. Methods In this retrospective multicenter cohort study, patients with large vessel occlusion were included, and those who underwent ADAPT versus SR first-pass thrombectomy (either as standalone or combined with aspiration) were compared. The primary outcome was a composite of first-pass effect (FPE, modified Thrombolysis In Cerebral Infarction (mTICI) 2c or better with one attempt) with no symptomatic intracranial hemorrhage (sICH). A causal forest model was used to estimate the conditional average treatment effect (CATE) for each patient, with larger CATEs indicating that ADAPT is expected to be more advantageous. Patients were stratified by CATEs, and outcomes were compared between treatment groups. Results Among 6700 included patients, ADAPT (n=3695, 55%) was associated with a higher rate of FPE with no sICH (39.9% vs 26.9%; adjusted OR (aOR) 2.07, 95% CI 1.77 to 2.41, P<0.001). The causal forest identified significant treatment effect heterogeneity (interaction P<0.001), where ADAPT was more advantageous in more recent years and among patients with M1 occlusions presenting in earlier time windows. Low-CATE patients showed no statistically significant difference between techniques (aOR 0.91, 95% CI 0.57 to 1.45, P=0.70), while medium- and high-CATE patients demonstrated progressively larger ADAPT advantages (aOR 2.06, 95% CI 1.67 to 2.55, and aOR 2.99, 95% CI 2.24 to 3.98, respectively, both P<0.001). Conclusions ADAPT may be superior to SR for a majority of patients, particularly in recent years, and among patients with M1 occlusions presenting in earlier time windows.

Automated diagnostic report generation lies at the core of clinical diagnosis and can alleviate clinician shortages. Existing diagnostic report generation methods have two major limitations: they rely on unimodal inputs (e.g., images), ignoring textual biomarkers like medical history, and lack proactive dialogue capabilities to elicit personalized clinical information. To address those issues, we propose a ProActive Multimodal Agentic (PAMA) system, which performs comprehensive disease analysis by examining biomarkers in diverse sources, including multi-view medical images, medical histories, and diagnostic conversations. Built upon a knowledge graph and recommendation-based dialogue architecture, PAMA actively initiates adaptive, multi-turn conversations with patients, which is integrated with visual data for robust and reliable report generation. Specifically, PAMA actively generates adaptive multi-turn questions to collect clinically relevant background information, and then fuses the resulting dialogue context with visual representations for robust diagnostic report generation. We validate our approach on two real-world benchmark datasets, MIMIC-CXR and IU-Xray, through extensive quantitative evaluations and comparisons with state-of-the-art baselines. Furthermore, we conduct user studies to assess the realism and clinical quality of the generated reports. Finally, we present real-world case studies to examine the performance of our system across diverse scenarios, demonstrating its robustness on scalability, complexity, and data variability.

ABSTRACT Purpose Despite 5‐year survival rates of over 90% among children and adolescents/young adults (CAYAs) with classic Hodgkin lymphoma (cHL), 15%–20% relapse after frontline therapy. Prior analysis of frontline Children's Oncology Group (COG) clinical trials demonstrated that, despite similar rates of relapse, non‐Hispanic Black (NHB) and Hispanic (vs. non‐Hispanic White [NHW]) patients experienced higher post‐relapse mortality. It is unknown whether post‐relapse disparities persist when second‐line treatment is delivered in a cooperative group trial setting. We examined overall survival (OS) by race and ethnicity in CAYAs enrolled in COG trials for relapsed/refractory (r/r) cHL. Methods A pooled analysis of individual‐level data from CAYAs (≤ 29 years) receiving therapy for r/r cHL on COG clinical trials (2001–2016) was conducted. The Kaplan–Meier method estimated 3‐year OS by racial and ethnic groups. Cox regression models examined associations of race and ethnicity and OS, adjusted for age, insurance, first versus ≥2 relapse, and time from initial diagnosis to relapse trial enrollment. Results Among 175 CAYAs treated on COG trials for r/r cHL (5.7% Asian or Pacific Islander, 14.9% Hispanic, 14.3% NHB, 61.7% NHW, 3.4% other), at median follow‐up of 4.9 years, 3‐year OS was 82.1% (95% confidence interval [CI], 75.3%–87.1%) and did not differ by race and ethnicity ( p = 0.36). In multivariable analyses, shorter time from diagnosis to relapse trial enrollment ( p = 0.01) and ≥2 relapses (vs. first, p = 0.004) conferred worse OS, with no significant effect of race and ethnicity ( p = 0.43). Conclusion Post‐relapse survival did not differ by race and ethnicity among CAYAs enrolled in COG trials for r/r cHL, suggesting access to clinical trials may mitigate OS disparities.