AGA Clinical Practice Update on Incorporating Functional Lumen Imaging Probe Into Esophageal Clinical Practice: Expert Review

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to summarize the available evidence and offer expert best practice advice on the incorporation of the functional lumen imaging probe (FLIP) into clinical practice, specifically its utility in the evaluation of esophageal symptoms, esophageal motor dysfunction, gastroesophageal reflux disease, and eosinophilic esophagitis.

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Early Vascular Aging Determined by 3-Dimensional Aortic Geometry: Genetic Determinants and Clinical Consequences

Circulation, Ahead of Print. BACKGROUND:Vascular aging is an important phenotype characterized by structural and geometric remodeling. Some individuals exhibit supernormal vascular aging, associated with improved cardiovascular outcomes; others experience early vascular aging, linked to adverse cardiovascular outcomes. The aorta is the artery that exhibits the most prominent age-related changes; however, the biological mechanisms underlying aortic aging, its genetic architecture, and its relationship with cardiovascular structure, function, and disease states remain poorly understood.METHODS:We developed sex-specific models to quantify aortic age on the basis of aortic geometric phenotypes derived from 3-dimensional tomographic imaging data in 2 large biobanks: the UK Biobank and the Penn Medicine BioBank. Convolutional neural ne2rk–assisted 3-dimensional segmentation of the aorta was performed in 56 104 magnetic resonance imaging scans in the UK Biobank and 6757 computed tomography scans in the Penn Medicine BioBank. Aortic vascular age index (AVAI) was calculated as the difference between the vascular age predicted from geometric phenotypes and the chronological age, expressed as a percent of chronological age. We assessed associations with cardiovascular structure and function using multivariate linear regression and examined the genetic architecture of AVAI through genome-wide association studies, followed by Mendelian randomization to assess causal associations. We also constructed a polygenic risk score for AVAI.RESULTS:AVAI displayed numerous associations with cardiac structure and function, including increased left ventricular mass (standardized β=0.144 [95% CI, 0.138, 0.149];P

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Unique Role of Intracellular Perinuclear β1-Adrenergic Receptors in Defining Signaling Compartmentation and Pathological Cardiac Remodeling

Circulation, Ahead of Print. BACKGROUND:β-Adrenergic receptors (βARs) are prototypical G protein–coupled receptors that regulate contractility in the normal heart and pathological remodeling in disease. Canonical βAR signaling originates at the plasma membrane, but functional βARs have been localized to intracellular membranes such as the endosome, sarcoplasmic reticulum, Golgi, and nuclear envelope. The functional significance of these intracellular receptors remains unclear, including whether they regulate cellular processes distinct from those regulated by plasma membrane receptors and whether they can be independently targeted for therapeutic benefit.METHODS:Live cell imaging of rat and human cardiomyocytes expressing novel compartment-specific modulators of βAR activity and fluorescent biosensors was used to study the compartment-specific βAR regulation of second messengers and to target enzyme activity. Compartmentalized signaling was compared with myocyte gene expression and hypertrophy. Adeno-associated virus gene delivery conferring gain and loss of perinuclear βAR activity was studied in wild-type mice and a mouse model of familial dilated cardiomyopathy.RESULTS:We demonstrate here that intracellular β1ARs present on Golgi membrane facing the outer nuclear membrane regulate a perinuclear cAMP compartment containing the A-kinase anchoring protein 6β signalosome, conferring selective regulation of perinuclear cAMP-dependent protein kinase activity independently of βARs at the plasma membrane or endosome. The A-kinase anchoring protein 6β compartment is shown to be of nanometer scale and dependent on local restriction of cAMP diffusion. In addition, perinuclear βARs are shown to be sufficient and necessary for activation of the Ca2+-dependent calcineurin–nuclear factor of activated T cells pathway and myocyte hypertrophy in vitro. Accordingly, adeno-associated virus 9–based delivery of an outer nuclear membrane–localized pepducin, which selectively activated perinuclear βARs in vitro, induced dilated cardiomyopathy in wild-type mice. Conversely, in vivo delivery of an outer nuclear membrane–localized nanobody, which selectively inhibited perinuclear βARs in vitro, improved cardiac function and inhibited pathological remodeling in a mouse model of familial dilated cardiomyopathy with established disease.CONCLUSIONS:These results demonstrate that β1ARs localized to Golgi membranes facing the outer nuclear membrane regulate A-kinase anchoring protein 6β signalosomes required for the induction of pathological cardiac remodeling, defining an intracellular nanocompartment. Proof of concept is provided for a novel therapeutic approach for familial dilated cardiomyopathy, with potential application to other forms of cardiovascular disease.

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PPARγ Agonists Accelerate MRI Signal Resolution Mediated by Resting-State Astroglia in Acute Intracerebral Hemorrhage

Stroke, Ahead of Print. BACKGROUND:In the aftermath of intracerebral hemorrhage (ICH), the clearance of harmful substances from the hematoma helps to mitigate brain edema and reduce the risk of subsequent neurological damage. This study aimed to investigate the mechanism underlying early hematoma processing following ICH and to explore the potential of modulating this process via astrocyte regulation.METHODS:ICH was induced by intrastriatal injection of bacterial collagenase. A calcium channel blocker, pyr3, was used to suppress astrocyte activity, or combined with PPARγ (peroxisome proliferator-activated receptor gamma) agonists (rosiglitazone and pioglitazone) as the intervention approach. The rats were randomly assigned to the following groups: ICH with vehicle treatment, ICH with pyr3 treatment, ICH with rosiglitazone treatment, ICH with pioglitazone treatment, ICH with pyr3 and rosiglitazone treatment, and ICH with pyr3 and pioglitazone treatment. Drugs were administered via the intraventricular route into the contralateral ventricle 10 minutes after ICH induction. The evolution of hematoma within the first 21 hours was meticulously examined using T2-weighted magnetic resonance imaging. Motor behavioral testing and diffusion-weighted imaging were used to assess longer-lasting functional outcomes and edema. To assess astrocyte-specific responses, an astrocyte cell line was incubated with hemin followed by different drug treatments. An intracellular hemin assay was used to quantify the hemin uptake capacity of astrocytes.RESULTS:Delayed signaling transitions of the hematoma were observed in the ICH with pyr3 treatment group in T2-weighted images, manifesting in different ICH models (ANOVA;P

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[News] Royal College of Obstetricians & Gynaecologists (RCOG) World Congress

The RCOG World Congress 2025 took place at the London ExCeL Centre on June 23–25, hosting over 2500 delegates from around 100 countries and delivering over 70 sessions with more than 220 global speakers. Under the theme of “Equity in care, innovation in action”, the programme covered an impressive range of topics, relevant to both UK and global audiences, including women’s health (eg, menopause, sexual health, inequalities in access to care, cancer, endometriosis, vulval disease, human papillomavirus (HPV) vaccination, and imaging in gynaecology), fertility and reproduction (eg, developments in assisted reproduction, abortion, and contraception), and pregnancy and post-partum care (eg, preterm birth, obstetric fistula, foetal imaging, and postpartum complications), as well as the emerging role of artificial intelligence (AI) and digital health across these topics.

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Mieloma multiplo di nuova diagnosi, progressione ritardata e più risposte profonde, confermate dalla PET, con la quadrupletta con isatuximab, anche nei pazienti con plasmacitomi. #EHA25 [Oncologia-Ematologia]

Nello studio registrativo IMROZ, una quota significativamente maggiore di pazienti con mieloma multiplo non eleggibili al trapianto autologo trattati in prima linea con la quadrupletta isatuximab-bortezomib-lenalidomide-desametasone (Isa-VRd) ha raggiunto la doppia negatività della malattia minima residua (MRD), misurata sia con il metodo convenzionale (NGS) sia attraverso l’imaging funzionale con PET/CT, rispetto ai pazienti trattati con la tripletta VRd.

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PASSIoN Trial (Perinatal Arterial Stroke Treated With Intranasal Stromal Cells): 2-Year Safety and Neurodevelopment

Stroke, Ahead of Print. BACKGROUND:The PASSIoN study (Perinatal Arterial Stroke Treated With Stromal Cells Intranasally) demonstrated the feasibility and short-term safety of single-dose allogeneic mesenchymal stromal cells (MSCs) administered intranasally to neonates with perinatal arterial ischemic stroke between February 2020 and April 2021. In this study, we assessed long-term safety and neurodevelopmental outcomes and explored outcome differences with a non–MSC-treated cohort.METHODS:In this post hoc analysis, we evaluated the safety of MSC administration by assessing brain tissue loss, adverse events, and neurodevelopmental outcomes of PASSIoN participants (n=10). The tissue loss ratio was calculated using semi-automatic segmentation based on neonatal and 3-month magnetic resonance imaging. At the age of 2 years, we assessed the occurrence of cerebral palsy, motor and cognitive delays (Zscore

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La remissione in Reumatologia tra clinica, imaging e percezione del paziente #EULAR2025 [Ortopedia e Reumatologia]

Negli ultimi anni, il concetto di remissione ha acquisito un valore strategico nella cura delle spondiloartriti e di altre malattie reumatologiche, Di questo tema ha parlato la prof.ssa Maria Antonietta d’Agostino (Direttore UOC Reumatologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma) nel corso del congresso EULAR e, in questa sede, proponiamo alcuni highlight emersi nel corso della sua relazione.

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Development and retrospective validation of an artificial intelligence system for diagnostic assessment of prostate biopsies: study protocol

Introduction
Histopathological evaluation of prostate biopsies using the Gleason scoring system is critical for prostate cancer diagnosis and treatment selection. However, grading variability among pathologists can lead to inconsistent assessments, risking inappropriate treatment. Similar challenges complicate the assessment of other prognostic features like cribriform cancer morphology and perineural invasion. Many pathology departments are also facing an increasingly unsustainable workload due to rising prostate cancer incidence and a decreasing pathologist workforce coinciding with increasing requirements for more complex assessments and reporting. Digital pathology and artificial intelligence (AI) algorithms for analysing whole slide images show promise in improving the accuracy and efficiency of histopathological assessments. Studies have demonstrated AI’s capability to diagnose and grade prostate cancer comparably to expert pathologists. However, external validations on diverse data sets have been limited and often show reduced performance. Historically, there have been no well-established guidelines for AI study designs and validation methods. Diagnostic assessments of AI systems often lack preregistered protocols and rigorous external cohort sampling, essential for reliable evidence of their safety and accuracy.

Methods and analysis
This study protocol covers the retrospective validation of an AI system for prostate biopsy assessment. The primary objective of the study is to develop a high-performing and robust AI model for diagnosis and Gleason scoring of prostate cancer in core needle biopsies, and at scale evaluate whether it can generalise to fully external data from independent patients, pathology laboratories and digitalisation platforms. The secondary objectives cover AI performance in estimating cancer extent and detecting cribriform prostate cancer and perineural invasion. This protocol outlines the steps for data collection, predefined partitioning of data cohorts for AI model training and validation, model development and predetermined statistical analyses, ensuring systematic development and comprehensive validation of the system. The protocol adheres to Transparent Reporting of a multivariable prediction model of Individual Prognosis Or Diagnosis+AI (TRIPOD+AI), Protocol Items for External Cohort Evaluation of a Deep Learning System in Cancer Diagnostics (PIECES), Checklist for AI in Medical Imaging (CLAIM) and other relevant best practices.

Ethics and dissemination
Data collection and usage were approved by the respective ethical review boards of each participating clinical laboratory, and centralised anonymised data handling was approved by the Swedish Ethical Review Authority. The study will be conducted in agreement with the Helsinki Declaration. The findings will be disseminated in peer-reviewed publications (open access).

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Potential Pitfalls In Bayesian Analysis for Child Abuse

No medical diagnosis is more fraught than child physical abuse. Implications are grave for the child, family, and community. If abuse is missed in its earliest stages, children may experience further injury, permanent disability, or death. If not present, an abuse diagnosis risks family disruption, lost trust, and delayed medical diagnoses. Abuse is not a single pathophysiological entity with consistent examination findings, laboratory results, natural history, or imaging. Unlike most pediatric illnesses, caregivers may resist diagnostic efforts, perhaps by providing information that is incomplete or misleading. The diagnosis is often challenged in legal proceedings, occasionally by deploying specious theories of causation with limited scientific support. When available, child abuse pediatricians, who have additional training and experience, can provide subspecialist consultation to address these challenges, but the diagnosis is also often first made by frontline clinicians.

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Memory Clinic Study Finds Lecanemab’s Adverse Events Manageable

Lecanemab became the first disease-modifying treatment for Alzheimer disease (AD) to receive traditional approval by the US Food and Drug Administration in 2023. Although the monoclonal antibody can remove amyloid-β plaques, the drug has been linked to brain changes known as amyloid-related imaging abnormalities (ARIA). A new study of patients with early symptomatic AD treated at an outpatient memory clinic suggests these and other adverse events are manageable in this population.

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Left Atrial Diverticula Detected on Cardiac CT in Patients With Acute Ischemic Stroke: A Substudy of Mind the Heart

Stroke, Ahead of Print. BACKGROUND:Left atrial (LA) diverticula are focal outpouchings of the LA wall and may increase ischemic stroke risk. We studied recurrent ischemic stroke in patients with acute ischemic stroke and LA diverticula detected on cardiac computed tomography.METHODS:We used data from a prospective cohort study of patients with acute ischemic stroke undergoing cardiac computed tomography acquired during the acute stroke imaging protocol. Cardiac radiologists systematically assessed the presence and characteristics of LA diverticula, defined as LA wall outpouchings with a length/ostium width ratio >0.5 and length ≥3 mm. We compared recurrent ischemic stroke and functional outcome (modified Rankin Scale) after 2 years between patients with and without LA diverticula, adjusting for age, history of atrial fibrillation and ischemic stroke, and anticoagulation use.RESULTS:Of 447 included patients (median age 72 [interquartile range (IQR), 62–81], 59% male), 126 (28%) had LA diverticula: median length 6 mm (IQR, 4–8), width 5 mm (IQR, 4–7), and volume 113 mm3(IQR, 52–254). There was no statistically significant difference in age (median 70 [IQR, 58–79] versus 73 [IQR, 63–81];P=0.06), sex (64% versus 57% male;P=0.28), history of ischemic stroke (21% versus 17%;P=0.48), atrial fibrillation (11% versus 19%;P=0.09), or baseline National Institutes of Health Stroke Scale score (median 5 [IQR, 2–14] versus 5 [IQR, 3–14];P=0.54) between patients with and without LA diverticula, respectively. Recurrent ischemic stroke was more common in patients with LA diverticula (18/124 [15%] versus 24/314 [8%], adjusted hazard ratio, 2.01 [95% CI, 1.08–3.77]), and recurrence risk increased with diverticulum volume (adjusted hazard ratio, 1.02 [95% CI, 1.01–1.03] per 10 mm3). Functional outcome was better in patients with diverticula (median modified Rankin Scale score of 2 [IQR, 1–3] versus 3 [IQR, 1–6], adjusted common odds ratio, 0.62, [95% CI, 0.42–0.92]).CONCLUSIONS:LA diverticula are a common finding on cardiac computed tomography in patients with acute ischemic stroke, and the risk of recurrent ischemic stroke was increased in these patients, particularly in those with larger diverticula. Atrial diverticula may be a risk factor for recurrent ischemic stroke.REGISTRATION:URL:https://www.onderzoekmetmensen.nl/nl/trial/50352; Unique identifier: NL6413901818.

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GRACE: protocol for a UK, secondary care, multicentre, assessor-blinded randomised controlled trial with a non-inferiority comparison to evaluate graduated compression stockings as an adjunct to extended duration pharmacological thromboprophylaxis for venous thromboembolism prevention

Introduction
Venous thromboembolism (VTE) occurs when a blood clot forms in a vein. It is comprised of deep vein thrombosis (DVT) and pulmonary embolism and can be potentially life-threatening. Patients undergoing surgery are at increased risk of developing VTE within hospital admission and 90 days after hospital discharge are collectively known as hospital-acquired thrombosis (HAT). Without the use of thromboprophylaxis, the untreated risk of VTE is reported to be as high as 40–60% in those undergoing major orthopaedic procedures and around 15–40% in the general surgical population.
HAT accounts for around 12 000 deaths per year in the UK. For patients undergoing surgery, there is good evidence for the use of thromboprophylaxis to prevent VTE.
Thromboprophylaxis is available in both pharmacological and mechanical forms. While there is a huge body of evidence demonstrating that pharmacological thromboprophylaxis significantly reduces VTE by 30–65%, the benefit of graduated compression stockings (GCS) has been called into question. The GRACE study (Graduated Compression stocking as an adjunct to Extended duration pharmacological thromboprophylaxis for venous thromboembolism prevention) aims to evaluate the adjuvant benefit of GCS in addition to extended duration pharmacological thromboprophylaxis (EDPTP) for elective surgical patients at highest risk of VTE.

Methods and analysis
GRACE is a pragmatic, multicentre randomised trial of adults undergoing surgery who are at high risk of VTE. Participants are randomised into a 1:1 ratio to either EDPTP and compression stockings (control arm) or EDPTP (intervention arm). Following randomisation, participants will undergo surgery and be followed up centrally at 7, 21–35 and 90 days after their procedure. All participants will be offered a bilateral full lower limb duplex scan at 21–35 days post procedure to capture any asymptomatic DVT.
The trial aims to randomise 8608 participants from around 50 National Health Service (NHS) and non-NHS sites in the UK over a 24-month period. The primary endpoint is any imaging-confirmed incidence of VTE within 90 days of surgery.

Ethics and dissemination
On 20 December 2023, GRACE received favourable ethical approval from the Wales Research Ethics Committee 3 Cardiff (23/WA/0350) and the Health Research Authority (IRAS 333539). The results of the study will be disseminated via peer-reviewed publications, presentation at national and international conferences and to study participants via electronic newsletter and social media channels.

Trial registration number
ISRCTN11667770.

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Early warning and stratification of the elderly cardiopulmonary dysfunction-related diseases: multicentre prospective study protocol

Introduction
In China, there is a lack of standardised clinical imaging databases for multidimensional evaluation of cardiopulmonary diseases. To address this gap, this study protocol launched a project to build a clinical imaging technology integration and a multicentre database for early warning and stratification of cardiopulmonary dysfunction in the elderly.

Methods and analysis
This study employs a cross-sectional design, enrolling over 6000 elderly participants from five regions across China to evaluate cardiopulmonary function and related diseases. Based on clinical criteria, participants are categorized into three groups: a healthy cardiopulmonary function group, a functional decrease group and an established cardiopulmonary diseases group. All subjects will undergo comprehensive assessments including chest CT scans, echocardiography, and laboratory examinations. Additionally, at least 50 subjects will undergo cardiopulmonary exercise testing (CPET). By leveraging artificial intelligence technology, multimodal data will be integrated to establish reference ranges for cardiopulmonary function in the elderly population, as well as to develop early-warning models and severity grading standard models.

Ethics and dissemination
The study has been approved by the local ethics committee of Shanghai Changzheng Hospital (approval number: 2022SL069A). All the participants will sign the informed consent. The results will be disseminated through peer-reviewed publications and conferences.

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