Citations

BACKGROUND AND OBJECTIVES Neonatal tracheal intubation is a high-risk procedure, and multiple attempts are associated with adverse events. At our tertiary neonatal intensive care unit, the baseline first-attempt success rate was 45%, which we aimed to increase to over 55% through a quality improvement (QI) initiative. METHODS A multidisciplinary team conducted a QI project using the define-measure-analyze-improve-control framework. Root cause analysis identified poor glottic visualization and patient instability as primary drivers of failure. Plan-do-study-act cycles were carried out (April 2023–July 2024), followed by a sustainability phase (August 2024–May 2025). Key interventions included the phased implementation of video laryngoscopy (VL) as the primary intubation device and the standardization of oxygenation during laryngoscopy using nasal high flow. First-attempt success was tracked using statistical process control, and bimonthly VL use was monitored as a process measure. RESULTS A total of 642 intubations were analyzed. By control chart analysis, the first-attempt success rate increased from a baseline of 45% to a sustained process mean of 61% during the intervention and sustainability phases. VL use increased from 0% at baseline to 70% to 90% during the sustainability phase. Success rates improved across all clinician types and locations. Notably, first-attempt success in infants weighing less than 1000 g increased from 38% at baseline to 62% during the intervention phase. CONCLUSION A systematic QI initiative focused on VL and standardized oxygenation improved and sustained neonatal intubation success rates, exceeding the project aim. The maintenance of high-success rates confirms the durability of these safety improvements.

ABSTRACT In 567 PH‐COPD patients from the PVRI GoDeep Meta‐Registry, ACE inhibitor use was associated with improved survival only in severe PH (PVR > 5 WU), supporting prospective trials targeting this high‐risk subgroup.

Abstract Cardiovascular disease is the leading cause of morbidity and mortality globally, imposing a substantial patient burden. Digital biomarkers derived from digital health technologies enable quantifiable, near-continuous, real-world capture of pathophysiological signals and are increasingly used across cardiovascular medicine. Their growth is often supported by big data analytics, artificial intelligence and connected sensors within the Internet of Things. This scientific statement systematically reviews digital biomarkers, their clinical utility across the cardiovascular care continuum, and summarizes major methodological and implementation challenges. We searched PubMed/MEDLINE, Embase and Scopus for phase III–IV cardiovascular trials published between 1 January 2019 and 1 August 2024 that collected digital biomarkers. We identified 541 records and included 32 trials (40 reports) enrolling 32 246 participants (44.71% women; mean age 66.2 ± 11.0 years). Heart failure was the most frequent target condition (16 trials, 50%), followed by cardiac implantable electronic devices trials (12 trials, 38%). Digital biomarkers included cardiac rhythm and heart rate, blood pressure, body weight, impedance-based measures, haemodynamic pressures, and physical activity and sleep patterns captured using diverse sensor technologies. Methodological quality was good (modal quality score 5; range 3–7), although most trials were unblinded. Current studies suggest potential clinical utility in selected cardiovascular conditions. Implementation remains challenging because of measurement variability, privacy and regulatory requirements, affordability and reimbursement barriers and inequities in access. Robust validation and outcome- and cost-effectiveness evidence are still needed. Registration number: CRD42024573879.

SUMMARY Aging is accompanied by profound changes in bladder function, leading to increased urinary frequency and incontinence that impair quality of life in humans and are recapitulated in mouse models. Bladder filling and emptying rely on precise mechanosensory feedback, yet how aging alters this sensory control remains unclear. PIEZO ion channels convert mechanical forces into cellular signals essential for bladder fullness sensation. Using inducible smooth-muscle specific Piezo1 deletion, we find that loss of Piezo1 attenuates aging-related bladder dysfunction. Dietary enrichment with margaric acid, a membrane-active fatty acid previously shown to inhibit PIEZO channels, reduced urinary dysfunction in aged mice. In humans, genotype–phenotype analyses reveal an association between a PIEZO1 gain-of-function variant and early-onset neuromuscular bladder dysfunction. Together, these findings define a smooth-muscle, PIEZO1-mediated mechanosensory basis for aging-related bladder dysfunction and introduce a non-invasive strategy for targeting PIEZO channels in vivo .

PURPOSE External beam radiation therapy (EBRT) has gained delayed acceptance as a recommended first-line treatment modality for patients with hepatocellular carcinoma (HCC), given limited evidence that it improves overall survival (OS). We analyzed individual patient data (IPD) from an international cohort to assess OS among patients with HCC treated with EBRT. METHODS We performed a systematic review of publications that assessed EBRT, met prespecified technical standards for HCC, and reported OS (search date December 15, 2022). Corresponding authors were invited to submit IPD for the study. We performed Kaplan-Meier survival analyses to determine OS and restricted mean survival time (RMST) stratified by Barcelona Clinic Liver Cancer (BCLC) stage and treatment status (ie, treatment-naïve and experienced). We performed random effects Cox proportional hazards modeling to assess clinical characteristics associated with OS. RESULTS Data were provided on 4,913 patients treated with EBRT with a median follow-up time of 5.0 years. The median OS was 6.8 years (95% CI, 5.7 to 8.7) for BCLC-0 and 4.6 years (95% CI, 4.1 to 5.1) for BCLC-A. Among treatment-naïve patients, the median OS was not reached (95% CI, 8.6 to not reached) for BCLC-0 and was 5.4 years (95% CI, 4.5 to 6.7) for BCLC-A. In multivariable models, more advanced BCLC stage, higher tumor burden, worse performance status, and Child-Pugh class B or C were associated with a higher risk of mortality. Ablative radiation dose and more recent year of treatment were associated with a reduced risk of death. CONCLUSION To our knowledge, this study represents the largest multinational cohort of patients with HCC treated with EBRT. OS outcomes with EBRT for very early- and early-stage HCC appear to be comparable with resection, thermal ablation, and other ablative locoregional therapies. These data support the inclusion of EBRT in the BCLC HCC clinical decision-making process.

Abstract Lentigo maligna (LM) is a subtype of cutaneous melanoma in situ that develops on chronically sun‐damaged skin in elderly individuals. Its diagnosis and management remain challenging due to its slow progression, frequent occurrence on cosmetically sensitive areas in frail individuals, and tendency for subclinical peripheral extension. Despite its potential for invasive transformation, the natural history of LM remains incompletely understood and evidence‐based management strategies for this specific entity remain limited. This work aims to bridge the gap between scarce high‐quality evidence and the clinicians' need for practical guidance on LM management by formulating evidence‐based and expert consensus‐driven recommendations for diagnosis, treatment and follow‐up. Under the coordination of the International Dermoscopy Society, a global, multidisciplinary consortium of 53 experts—including dermatologists, dermato‐oncologists, dermatologic surgeons, radiologists, radiotherapists, pathologists and epidemiologists—formulated recommendations through structured consensus, informed by a comprehensive review of current scientific evidence and clinical practice standards. Optimal management of LM requires accurate diagnosis and individualized treatment planning. Non‐invasive skin imaging techniques, especially dermoscopy and reflectance confocal microscopy, aid in diagnosis, biopsy orientation, lesion delineation and post‐treatment monitoring. Multiple partial biopsies help confirm diagnosis and rule out invasion. Complete surgical excision remains the first treatment option. No definitive safety margins can be recommended for standard surgery; margin‐controlled techniques are preferable for large or ill‐defined lesions. Topical imiquimod and radiotherapy are effective alternatives where surgery is unsuitable. Topical imiquimod is useful as primary, adjuvant or neoadjuvant therapy. Blind destructive methods should be avoided. Close clinical and imaging follow‐up is needed. Patient‐centred care, shared decision‐making, and a multidisciplinary approach are critical for optimal outcomes. These international consensus recommendations summarize current best practices for LM management, offering practical, evidence‐informed guidance to clinicians while acknowledging the potential of future research in refining these conclusions.

PURPOSE STELLAR (ClinicalTrials.gov identifier: NCT02796261 ) was a phase III, randomized, open-label trial of eflornithine + lomustine versus lomustine monotherapy in patients with recurrent grade 3 astrocytoma. METHODS At trial initiation, eligibility criteria included: age ≥18 years, anaplastic astrocytoma (2016 WHO CNS Tumor classification [WHO CNS4]), first recurrence ≥6 months after radiation and temozolomide (TMZ), Karnofsky performance status ≥70, and no imaging findings consistent with grade 4 glioblastoma. Random assignment (1:1) was stratified by isocitrate dehydrogenase ( IDH ) mutation, age, resection extent, and geography. Patients received eflornithine (2.8 g/m 2 orally, every 8 hours [2 weeks on, 1 week off]) + lomustine (90 mg/m 2 orally, once every 6 weeks), or lomustine monotherapy (110 mg/m 2 once every 6 weeks). The primary end point was overall survival (OS). RESULTS Among 343 patients randomly assigned across 74 sites in eight countries, there was no difference in survival between eflornithine + lomustine and lomustine monotherapy (median OS 23.4 v 20.3 months, hazard ratio [HR], 0.94). Following changes in classification and grading in the 2021 WHO CNS5, a subset analysis of patients with IDH- mutant, grade 3 astrocytoma (n = 196), defined in 2024, before unblinding, showed clinically meaningful improvements in median OS with eflornithine + lomustine versus lomustine monotherapy (34.9 v 23.5 months, HR, 0.64) and median progression-free survival (PFS, 15.8 v 7.2 months, HR, 0.57). No differences were observed among patients with CNS grade 4 disease. Grade ≥3 treatment-emergent adverse events of relevance were related to reversible myelosuppression (eflornithine + lomustine 42% v lomustine monotherapy 29% of patients) and hearing impairment (24% v 0%). No new safety signals were identified. CONCLUSION Clinically meaningful improvements were observed; eflornithine + lomustine doubled PFS and improved OS in patients with recurrent IDH -mutant, grade 3 astrocytoma, but not grade 4 tumors, after prior radiotherapy and TMZ, consistent with its cytostatic mechanism of action.