Citations

ABSTRACT We report on the 2025 International ICU Diary Conference that provided a comprehensive update on current knowledge, innovations and global practices related to ICU diaries. Held in a 6‐week online format, the event featured 23 speakers and was attended by mean 69.7 (SD 20.5) participants per session. Topics included development of ICU diaries, use in special settings, digital diaries, survivors' and families' experiences, Post‐Intensive‐Care Syndrome and follow‐up and implementation projects. Highlights were innovative solutions for digital diaries and the report of persons with lived and living experiences with diaries, changing the focus on humanising critical care. Relevance for Practice ICU diaries support patient‐ and family‐centred care and should be implemented more widely across healthcare systems. Their successful adoption requires contextual adaptation and policy support, with future development likely to be shaped by the increasing use of digital ICU diaries.

Purpose: An Adult Cochlear Implant Aural Rehabilitation Special Interest Group was formed in 2023. Members represent interdisciplinary collaborators, including audiologists, speech-language pathologists, surgeons, nonclinical administrators, manufacturer/industry representatives, and researchers. Current perspectives of adult cochlear implant (CI) recipients regarding aural rehabilitation (AR) remain unknown and understudied. The aim of this study is to survey adult CI recipients to determine their perspectives on the AR process. Method: A web-based national survey was sent to adult CI recipients through multiple channels. The survey asked recipients about their demographics, state of residence, hearing loss history, and device configuration. Questions probed recipients' experiences of learning about AR options, services used, definitions of AR, and perceived value of services received. Questions were also asked about barriers to AR services, preoperative counseling, and satisfaction with their decision to pursue a CI. Results: A total of 115 CI recipients responded to the survey. Results revealed a relative lack of information provided to many CI recipients regarding AR services. Many CI recipients reported wishing they had received additional resources in the areas of music training and equipment troubleshooting. Most participants reported that both one-on-one clinician-guided AR and independent listening practice were effective methods of AR. Conclusions: Findings shed light on current gaps in providing the most effective AR services, which will need to be addressed to optimize hearing health care and outcomes for adult CI recipients. Future work should include outreach to a broader representation of CI users to expand our understanding of AR resources, education, and limitations.

Purpose: While acquired apraxia of speech (AOS) has been the focus of intervention research for decades, little information is reported about the demographic representation of study participants. This article examines the extent to which published AOS treatment studies report participants' age, sex/gender, race/ethnicity, language background, and socioeconomic status; identifies critical gaps in the literature; and considers implications for representativeness. This information supports the important call to capture these patient factors systematically and thereby advance equity in research and clinical care. Method: This study is part of a larger systematic review examining treatment outcomes for acquired AOS. A comprehensive search of databases from 1951 to April 2024 was completed to determine the proportion of treatment articles that reported demographic information related to diversity. Studies were reviewed by trained raters using a standardized data extraction protocol with a consensus protocol. Results: While participant age and sex/gender were reported in nearly all studies (99% and 100%, respectively), only 24% of studies reported on race/ethnicity, 15% provided information on participants' language background, and none reported socioeconomic status. Among studies that included race/ethnicity, 89% of the participants were White, with minimal representation of other racial/ethnic groups. Conclusions: The underreporting of race/ethnicity, language background, and socioeconomic factors limits the generalizability and ecological validity of AOS treatment research. The field must prioritize inclusive participant recruitment and consistent demographic reporting. We propose a practical template for use in both research and clinical contexts to support more thorough data collection and to inform future work in diagnosis, assessment, and intervention for AOS. Supplemental Material: https://doi.org/10.23641/asha.31172353

Background and Aims: Cholangiocarcinoma (CCA) is a rare but aggressive malignancy with poorly understood genetic susceptibility. To date, genome-wide association studies (GWAS) investigating germline variants associated with CCA risk remain limited. We aimed to identify genetic risk loci for CCA and its clinical subtypes through comprehensive GWAS and post-GWAS analyses. Approach and Results: We conducted a GWAS of 2366 CCA cases and 11,750 controls of European ancestry. Genome-wide significant loci ( p <5×10 −8 ) were identified and further examined through fine-mapping, functional annotation, and HLA imputation. Subgroup analyses were conducted by CCA subtypes and primary sclerosing cholangitis (PSC) status. Cross-trait linkage disequilibrium score regression and Mendelian randomization were employed to investigate the shared genetic architecture and potential causal relationships with a diverse range of traits. We identified 1 new genome-wide significant variant, rs535777 (OR=1.44), near HLA-DRB1/DQA1 associated with CCA, and 2 variants associated with extrahepatic CCA: rs116224263 (OR=0.17) in LINC02506 at 4p15.1 and rs6914950 (OR=1.63) near HLA-DRB1/DQB1 . Stratified analyses revealed rs2395184 (OR=3.51) near HLA-DRA/DRB5 associated with PSC-related CCA, and rs142674434 (OR=2.98) in THSD7A at 7p21.3 associated with non-PSC-related CCA. HLA imputation uncovered new amino acid residues associated with disease risk. Cross-trait analyses identified shared genetic signals between CCA and anthropometric, lipidemic, lifestyle, and medical traits. Mendelian randomization supported putative causal associations for 12 traits with CCA or its subtypes. Conclusions: Our large-scale GWAS highlights new genetic variants and HLA-linked mechanisms underlying CCA susceptibility. Integrating multi-step post-GWAS approaches enhances understanding of CCA pathogenesis and may facilitate the development of risk biomarkers for early detection and precision prevention strategies.

Abstract Secondary central nervous system (CNS) large B-cell lymphoma (SCNSL) occurs in the de novo setting, as a CNS-isolated relapse, or synchronous (concomitant CNS and systemic) relapse. SCNSL is a devastating event without therapeutic consensus. Thus, we aimed to evaluate treatment outcomes in an international cohort. Progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR, estimated using competing-risk models) were reported. Prognostic factors were identified in a 6-month landmark multivariate analysis. Outcomes after thiotepa autologous stem cell transplant (ASCT) and chimeric antigen receptor (CAR) T-cell therapy (CAR-T) delivered at relapse were compared after propensity score matching (PSM). A total of 1139 patients were included in the analysis (de novo: 537; relapsed SCNSL: 602). Two-year PFS estimates were 40.4%, 43.9%, and 16.2% for de novo SCNSL, CNS-isolated relapse, and synchronous relapse, respectively. Patients with CNS-isolated relapse demonstrated low rates of systemic recurrence (24-month CIR, 6%). Thiotepa-ASCT correlated with longer survival in de novo SCNSL (PFS: hazard ratio [HR], 0.57; P = .005; and OS: HR, 0.62; P = .023) and CNS-isolated relapses (PFS: HR, 0.55; P = .002; and OS: HR, 0.39; P&lt; .0001). ASCT (thiotepa or no thiotepa) also associated with improved survival in synchronous relapses (PFS: HR, 0.57; P = .023; and OS: HR, 0.48; P = .019). Higher survival with thiotepa-ASCT than CAR-T was observed after PSM (PFS: HR, 0.45; P = .005 and OS: HR, 0.41; P = .014). These data support thiotepa-ASCT in eligible patients, particularly de novo disease and CNS-isolated relapses. CNS-isolated relapse was infrequently associated with systemic recurrence, supporting treatment regimens adopted from primary CNS lymphoma.

Abstract Purpose: Mutant IDH1 (mIDH1) defines a therapeutically targetable subtype of intrahepatic cholangiocarcinoma (ICC), with the mIDH1 inhibitor ivosidenib approved for advanced disease. A subset of patients experiences prolonged disease stabilization; however, the molecular basis for eventual progression remains poorly defined. Experimental Design: We performed molecular profiling of matched baseline and postprogression circulating tumor DNA (ctDNA) samples from patients with mIDH1 ICC enrolled in the ClarIDHy phase III trial. Functional studies were conducted to characterize candidate resistance mechanisms. Results: Longitudinal ctDNA analysis of 18 patients treated with ivosidenib for &gt;6 months revealed emergent genomic alterations in multiple cases. Acquired mutations in mitogen-activated protein kinase (MAPK) pathway genes (KRAS, NRAS, MAP2K1, NF1) were identified in five cases, with instances of concurrent alterations and/or high variant allele fractions (VAF). Additional candidate resistance events included a secondary IDH1 mutation and a hotspot IDH2 mutation, detected at low VAF in the same patient. Functional studies showed that these IDH mutations conferred sustained 2-hydroxyglutarate production and ivosidenib resistance, whereas MAPK activation blunted gene expression induced by ivosidenib plus IFNγ, a key therapeutic output of mIDH1 inhibition. In parallel, baseline ctDNA profiling of 81 patients revealed that ARID1A mutations and elevated mIDH1 VAF were associated with reduced clinical benefit. Conclusions: MAPK pathway alterations represent a recurrent mechanism of resistance to mIDH1 inhibition in ICC, whereas emergent IDH1/IDH2 mutations appear infrequent. Functional data suggest that MAPK-mediated resistance may involve impaired IFN signaling. These results support MAPK-directed combination strategies and highlight the utility of ctDNA profiling to identify predictive and resistance biomarkers in mIDH1-driven ICC.

Abstract Background Early mechanisms of neuronal damage in Alzheimer's Disease (AD) include mitochondrial dysfunction and abnormal energy homeostasis. AD‐associated mitochondrial signaling was shown to occur upstream of amyloid precursor protein processing, Ab production, apolipoprotein E (APOE) expression, and tau pathology. However, whether alterations in mitochondrial function are sufficient to instigate AD remains unclear. Mitochondrial complex I (mtCI) is a rate‐limiting enzyme in the oxidative phosphorylation (OXPHOS) machinery. Changes in mtCI activity influence ATP and ROS production, cellular energy and redox homeostasis. We examined how reduced activity of mtCI due to a knockout of one of its accessory subunits Ndufs4 in mice affects transcriptional networks in the brain. We also determined whether reduced activity of mtCI abrogates neuroprotective properties of a small molecule CP2. Method RNA‐sequencing of the brain tissue was performed using Ndufs4 ‐/‐ and control mice ( n = 3–5 per group). The co‐expression modules of differentially expressed genes were compared to the AMP‐AD patient cohort data. Key mechanisms, including mitophagy signaling, were confirmed using ELISA and western blot analyses; the effect on mtCI activity was confirmed using functional assays. Results In Ndufs4 ‐/‐ mice, a residual activity of mtCI was ∼50% of the control. This loss of function led to a global disruption of mitochondrial homeostasis, energy metabolism, synaptic function, significant increase in mitophagy and a reduction in biogenesis. Transcriptomic signatures in brain tissue of male and female Ndufs4 ‐/‐ mice overlapped with changer reported for AD patients and AD mouse models with Ab and p ‐tau pathologies. These changes were partially rescued by a neuroprotective mitochondria‐targeting small molecule CP2. Consistent with studies in AD mice, CP2 treatment in Ndufs4 ‐/‐ mice augmented the expression of genes associated with mitochondrial biogenesis and turnover, synaptic activity, autophagy, redox balance, and reduced expression of genes related to inflammation. Sex‐specific differences included better adaptation to a reduced activity of mtCI and to CP2 treatment in female mice. Conclusion Reduced mtCI activity was sufficient to induce the AD‐like transcriptomic changes in brain. Residual mtCI function was sufficient to mediate neuroprotective effect of CP2, emphasizing a key role of mitochondria in AD development and treatment.

Abstract Background Eligibility criteria for clinical trials are crucial for maintaining safety and study integrity. However, overly restrictive criteria can result in unrepresentative trial populations, leading to gaps in understanding real‐world treatment efficacy. Addressing potentially modifiable exclusions (PMEs) could enhance trial accessibility and participation without compromising safety. Methods The authors retrospectively analyzed screen‐failed patients with biliary tract cancer or pancreatic cancer between August 2019 and November 2024 at The University of Texas MD Anderson Cancer Center. Screen‐failed patients were those who provided informed consent but did not participate for any reason. Clinical data were obtained from screening logs and electronic health records. PMEs were identified and validated by two independent medical oncologists. Results Of 585 screen‐failed patients from 18 trials, 509 were analyzed (367 with pancreatic cancer and 142 with biliary tract cancer) after excluding 76 because of incomplete data. Leading causes of screen failure were declined participation (19%), comorbidities (12%), suboptimal organ function (11%), absence of a biomarker (10%), and insufficient biospecimens (7%). Reasons for declining included preference for standard care (23%), travel (22%), and competing trials (5%). The authors identified 69 patients (13.6%) who had PMEs (primarily borderline laboratory abnormalities), including liver function (23%), kidney function (20%), platelet count (12%), hemoglobin (7%), and white blood cell count (6%) abnormalities. Other PMEs included previous or concurrent malignancies (9%) and viral hepatitis (4%). PMEs were evenly distributed across trials. Conclusions Rigid eligibility criteria exclude stable patients who might benefit from investigational treatments. Easing criteria related to incidental or asymptomatic laboratory abnormalities could broaden trial accessibility and improve enrollment in populations that are more representative of real‐world use.