Citations

Importance An estimated 70% to 80% of older adults develop delirium in the intensive care unit (ICU). Objective To determine if a slow-tempo music (60-80 beats/min) listening intervention decreases delirium duration, delirium severity, pain, or anxiety in older adults undergoing mechanical ventilation. Design, Setting, and Participants This multicenter randomized clinical trial with concealed outcomes assessments was conducted in older adults undergoing mechanical ventilation from February 2020 to December 2023. Patients were enrolled from the ICUs of 2 hospitals affiliated with the Indiana University School of Medicine and from the Mayo Clinic in Rochester, Minnesota. Intervention A music intervention comprising classical and contemporary tracks, delivered twice daily through noise-canceling headphones and tablets for up to 7 days, was compared to active control listening to a silence track delivered under identical conditions. Main Outcomes and Measures The primary outcome was delirium/coma-free days during the 7-day intervention period assessed by the Confusion Assessment Method for the ICU (CAM-ICU) and the Richmond Agitation-Sedation Scale. The secondary outcomes were delirium severity assessed by the CAM-ICU-7, pain assessed by the Critical Care Pain Observation Tool, and anxiety assessed by the visual analog scale for anxiety (VAS-A). Results A total of 158 patients were randomized (mean [SD] age, 68 (9.2) years; 72 [45.5%] female and 86 [54.4%] male). In an intention-to-treat analysis, no differences were found in the number of delirium/coma-free days in the music intervention group compared with control (median [IQR] days, 2.5 [0-5] vs 3 [0-5]; P = .66). There were also no statistically significant differences in the mean CAM-ICU-7 scores, mean pain scores, or mean VAS-A scores over the 7-day intervention period. By end of the 7-day period, both music intervention and control groups had similar mean (SD) CAM-ICU-7 scores (2.72 [2.80] vs 2.56 [2.72]), Critical Care Pain Observation Tool scores (0.20 [0.55] vs 0.61 [1.29]), and VAS-A scores (43.6 [24.7] vs 28.8 [38.4]). Conclusions and Relevance In this randomized clinical trial among older adults undergoing mechanical ventilation, a slow-tempo music intervention did not demonstrate a statistically significant decrease in delirium duration, delirium severity, pain, or anxiety symptoms. Trial Registration ClinicalTrials.gov Identifier: NCT04182334

This cohort study evaluates the use of arterial spin labeling magnetic resonance imaging (ASL MRI) to quantify placental perfusion in pregnant individuals with a fetus with congenital heart disease.

Objectives: Participant retention is essential in prospective studies to minimize bias and maintain validity. This study aimed to estimate retention rates and identify factors influencing attrition in a multicenter cohort (PROCEED) of US adults with acute/recurrent acute pancreatitis (AP/RAP) and chronic pancreatitis (CP). Methods: Participants from the PROCEED study with AP/RAP or CP eligible for follow-up within the designated visit window were included. Retention was defined as completing at least one follow-up visit during the observation period. Retention was analyzed by follow-up mode (in-person and/or medical record review) and disease type (AP/RAP and CP). Retention factors were assessed using univariate analyses (Wilcoxon rank-sum for continuous variables, χ 2 /Fisher's exact for categorical) and multivariable logistic regression. Missing data were adjusted using multiple imputations in statistical modeling. Results: Among 1279 participants (AP/RAP: n=632, median age 47, 48.9% female; CP: n=647, median age 54, 46.5% female), we observed high cumulative and annualized retention rates, with improved retention when incorporating medical record reviews. In multivariable regression analyses, older age was statistically significantly associated with in-person retention in the AP/RAP group ( P =0.0001), while a higher self-reported physical health (assessed with PROMIS Global Health Physical Health T-score) was a key predictor of retention in CP ( P =0.034). Conclusions: Integrating medical records review substantially enhanced retention rates, enabling robust analyses of pancreatitis outcomes and disease progression. Older age and better self-reported physical health were key predictors of retention, highlighting the need for targeted strategies to enhance engagement among younger participants and those with poorer health in long-term studies.

Background Carpal tunnel release (CTR) is one of the most frequently performed procedures in the United States, with both open (OCTR) and endoscopic (ECTR) techniques widely used. As surgical practices evolve and outpatient care expands, understanding future utilization trends across care settings is increasingly important. This study projects the use of OCTR and ECTR through 2040 to inform shifting surgical preferences and healthcare demands. Methods This study analyzed procedural data from 2010 to 2019 using the PearlDiver Mariner all-payer claims database. Cases of OCTR and ECTR were identified using Current Procedural Terminology codes. Procedures were further stratified by inpatient or outpatient status based on the documented site of service field within the database. Log-linear, Poisson, negative binomial regression, and autoregressive integrated moving average (ARIMA) models were applied to procedural volumes to project trends through 2040. The ARIMA model was selected based on the lowest normalized root mean square error and overall model performance. Results In 2019, there were 31,190 outpatient ECTR, 155 inpatient ECTR, 101,334 outpatient OCTR, and 1359 inpatient OCTR procedures. By 2040, outpatient ECTR is projected to grow to 65,072 cases (95% CI, 62,471–67,781) at 3.79% annually. Inpatient ECTR is projected to reach 181 cases (95% CI, 97–340) with 2.13% annual growth. Outpatient OCTR is expected to decline to 77,834 cases (95% CI, 76,287–79,413), and inpatient OCTR to 962 cases (95% CI, 809–1143), with annual decreases of 1.19% and 1.48%, respectively. Conclusions By 2040, demand for outpatient ECTR is projected to increase by 110.31% compared to 2019, whereas outpatient OCTR is expected to decline by 20.31%. Although inpatient utilization remains limited, the adoption of endoscopic techniques is anticipated to rise across all care settings, in contrast to the continued decline of open procedures. These trends highlight the ongoing shift toward minimally invasive, ambulatory surgical care. Strategic planning in surgical training, healthcare infrastructure, and reimbursement models will be critical to meet changing demands. Further research is needed to validate these projections in broader populations and across diverse healthcare systems.

Stiff Person Syndrome (SPS) is a rare, progressive autoimmune neurological disorder characterized by painful spasms, muscle rigidity, and heightened sensitivity to external stimuli. Management often relies on therapies that fall outside standard hospice formularies, creating challenges in end-of-life care for affected individuals. We present the case of a 57-year-old woman with metastatic colorectal cancer and SPS whose primary concern in transitioning to hospice was the risk of symptom destabilization if standard neurological treatments, including intravenous immunoglobulin and intrathecal baclofen, were discontinued. Through close interdisciplinary collaboration among palliative care, neurology, and the hospice team, an individualized plan of care was developed that preserved access to symptom-modifying treatments while aligning with the hospice philosophy. Environmental and pharmacologic strategies—including diazepam, levetiracetam, and anticipatory planning—were employed to address evolving symptoms, resulting in effective symptom control and avoidance of hospital readmission. This case highlights the need for flexible, patient-centered approaches in hospice care for rare neurological conditions like SPS. Continuation of disease-specific therapies for symptom palliation can be ethically and clinically appropriate when integrated with clear goals of care. Adaptable interdisciplinary models are essential to attend to quality of life and support care that is in alignment with patient values at the end of life.

Abstract Rehabilitation after musculoskeletal trauma is globally acknowledged as essential for restoring function and improving quality of life; however, significant variation exists in rehabilitation frameworks and services worldwide. Although certain principles—such as early intervention, structured care pathways, and multidisciplinary approaches—are universally recognized as important determinants of outcomes in trauma patients, their implementation and effectiveness vary considerably due to differences in health care infrastructure, economic resources, policy frameworks, and cultural contexts. Drawing on comparative analyses of rehabilitation frameworks across regions, including North America, Latin America, Europe, Asia-Pacific, and Africa, this paper identifies structural variations, systemic challenges, and innovations that can inform global rehabilitation efforts. Strategic international collaboration focusing on shared learning, standardized protocols, technology integration, and targeted investments is key to creating equitable and sustainable rehabilitation models, especially in resource-limited settings and aging populations.

Radiology is undergoing a paradigm shift from traditional single-function AI systems to sophisticated multi-agent networks capable of autonomous reasoning, coordinated decision-making, and adaptive workflow management. These agentic AI systems move beyond simple pattern recognition to encompass complex radiological workflows including image analysis, report generation, clinical communication, and care coordination. While multi-agent radiological AI promises enhanced diagnostic accuracy, improved workflow efficiency, and reduced physician burden, it simultaneously amplifies the long-standing “black box” problem. Traditional explainable AI methods, which are adequate for understanding isolated diagnostic predictions, fail when applied to multi-step reasoning processes involving multiple specialized agents coordinating across imaging interpretation, clinical correlation, and treatment planning. This paper examines how agentic AI systems in radiology create “compound opacity” layers of inscrutability from agent interactions and distributed decision-making processes. We analyze the autonomy–transparency paradox specific to radiological practice, where increasing AI capability directly conflicts with interpretability requirements essential for clinical trust and regulatory oversight. Through examination of emerging multi-agent radiological workflows, we propose frameworks for responsible implementation that preserve both diagnostic innovation and the fundamental principles of medical transparency and accountability.

Patient-derived organoids (PDOs) have emerged as powerful tools in personalized medicine applicable to both non-malignant conditions and to cancer, where they are increasingly used for personalized drug screening and precision treatment strategies in part due to their ability to replicate tumor heterogeneity. They also serve as study model systems to understand disease mechanisms, pathways, and the impact of ex vivo exposures. We present a detailed step-by-step protocol for generating organoids from normal crypts, polyps, and tumors, including methods for tissue processing, crypt isolation, culture establishment, and the transition from basolateral to apical-out polarity for co-culture and exposure-based studies. The protocol also includes immunofluorescence staining procedures for cellular characterization and quality control measures. Our standardized approach successfully generates organoids from diverse colorectal tissues with high efficiency and reproducibility. This comprehensive guide addresses common technical challenges and provides troubleshooting strategies to improve success rates across different sample types. We believe that this resource will enhance reproducibility in organoid research and expand their utility in translational applications, particularly for personalized medicine approaches in colorectal cancer.

Background The purpose of this study was to clarify the usefulness of the ‘hot cross bun’ sign (HCBS) as a diagnostic imaging marker in a large cohort of patients with multiple system atrophy (MSA) and spinocerebellar ataxia (SCA). Methods This multicentre study included 97 patients with neuropathologically confirmed MSA, and 105 patients with genetically confirmed SCA. Neuroimaging features, including HCBS and middle cerebellar peduncle (MCP) hyperintensities, were assessed. HCBS was graded from 0 to 2: 0, none; 1, only a vertical hyperintense line; and 2, a cruciform hyperintense line. The neuropathological correlates of HCBS were evaluated in 15 patients with MSA with ≤3 months between MRI and autopsy. Results In patients with a disease duration <3 years, grade 1 or 2 HCBS was detected in 100% patients with MSA with predominant cerebellar ataxia (MSA-C) and 39.0% with SCA; whereas grade 2 HCBS was observed in 50% with MSA-C and 2.4% with SCA. Moreover, the coexistence of grade 2 HCBS and MCP hyperintensities exhibited a specificity of 100%. A neuropathological assessment revealed myelin loss, alpha-synuclein aggregates and astrocytic reaction in the MCP, transverse fibres, central zone between longitudinal fasciculi and raphe nucleus, with relative preservation in the longitudinal fasciculi and medial lemniscus in patients with MSA and grade 2 HCBS. Conclusions Grade 1 or 2 HCBS is a highly sensitive finding in patients with MSA-C, and the observation of grade 2 HCBS within 3 years of motor symptom onset has excellent specificity for discriminating MSA-C from SCA, especially when accompanied by MCP hyperintensities.

Objective To investigate the diagnostic performance of perilesional biopsies (PLBx) compared to other biopsy strategies, assessing the impact of the Prostate Imaging‐Reporting and Data System (PI‐RADS) score and biopsy history in patients with a visible lesion at multiparametric magnetic resonance imaging of the prostate (mpMRI), as the European Association of Urology guidelines recommend combining MRI‐targeted biopsies (TBx) with PLBx as an alternative to systematic biopsies (SBx) even though evidence is limited. Patients and Methods We relied on a cohort of 2852 patients with PI‐RADS ≥3 lesions undergoing TBx + SBx at three tertiary referral centres. The primary outcome was detection of clinically significant PCa (csPCa) (International Society of Urological Pathology Grade Group [ISUP GG] ≥2) of TBx + PLBx vs TBx + SBx. Results were stratified by PI‐RADS score and biopsy history. The PLBx cores were defined as samples taken from prostate sectors adjacent to the mpMRI lesion. We finally assessed insignificant PCa (insPCa, i.e., ISUP GG 1) detection across biopsy strategies. Differences were assessed using the chi‐square test. Results Detection of csPCa was 48%. Overall, TBx + SBx had a higher csPCa detection rate than TBx + PLBx (50% vs 45%, P = 0.03), particularly in PI‐RADS 3 lesions (26% vs 21%, P = 0.02) and active surveillance (AS) patients (46% vs 40%, P = 0.04). No significant differences were found in PI‐RADS 4 (53% vs 50%, P > 0.1) or PI‐RADS 5 (76% vs 75%, P > 0.1). In the biopsy naïve and previous negative biopsy groups, csPCa detection was similar between strategies ( P > 0.1). Conclusions Overall, TBx + SBx offers the highest detection of csPCa. Even though TBx + PLBx may be considered in PI‐RADS 4–5 lesions to reduce insPCa detection, TBx + SBx remains the preferred strategy for PI‐RADS 3 and AS patients.