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The prevalence of mechanical complications following acute myocardial infarction has steadily declined in recent years owing to advances in prompt coronary revascularization, and they now occur in <1% of acute myocardial infarction cases. Nevertheless, significant haemodynamic impairment may already be present at hospital admission, requiring immediate diagnostic evaluation and urgent intervention. Until recently, surgical repair was the only treatment option, with non-negligible in-hospital mortality rates, particularly among patients with acute cardio-circulatory failure. Advances in transcatheter percutaneous procedures have now introduced alternative treatment strategies, especially for high-risk or inoperable patients. Recurrence of post-acute myocardial infarction mechanical complications, even shortly after the repair of the underlying lesion, has a critical impact on patient outcome and underscores the need for careful monitoring during hospitalization as well as after discharge. The role of concomitant coronary revascularization remains controversial, with variable effects on both early and late outcomes, and warrants further investigation. Temporary mechanical circulatory support has shown encouraging results, either for pre-procedural haemodynamic stabilization ('bridge-to-procedure') or for prophylactic, extended peri-procedural support to facilitate myocardial recovery ('bridge-to-recovery'). Optimal management should be guided by a multidisciplinary Heart Team approach (including Shock Team involvement where appropriate) with integration of palliative care into the decision-making process.

Emergency nurses must be proficient in operating the Level-1 rapid infusion system to manage hypovolemic shock effectively. However, training opportunities for this infrequently used but life-critical device remain scarce, owing to resource constraints and limited access to equipment. Augmented reality (AR) has emerged as a promising educational technology that provides immersive, hands-on learning experiences without compromising patient safety; yet its application to specialized medical device training in nursing has not been rigorously evaluated. This study aimed to evaluate the effects of an AR-based training program using Microsoft HoloLens 2 on emergency nurses' clinical competency, self-efficacy, and educational satisfaction in operating the Level-1 rapid infusion system, compared with traditional guideline-based self-directed learning. A posttest-only randomized controlled trial was conducted at Samsung Medical Center in Seoul, Republic of Korea. Between July 17 and July 20, 2023, 42 registered nurses with no prior Level-1 experience were enrolled and randomly assigned in a 1:1 ratio to an experimental group receiving AR-based training on a single HoloLens 2 device (n=21) or a control group performing self-directed learning from a printed manual (n=21). Clinical competency was assessed by time (learning and performance), accuracy (a manufacturer-aligned checklist scored out of 100, and an expert-validated 22-step pass or fail evaluation), and the number of assistance requests. Self-efficacy (6-item scale; Cronbach α=0.80) and educational satisfaction (4-item scale; Cronbach α=0.87) were measured by questionnaire. Because most outcomes were non-normally distributed, groups were compared using the Mann-Whitney U test, with data reported as medians and IQRs. Learning time was longer in the experimental group (median 18.20, IQR 15.48-21.67 vs 8.98, IQR 5.85-11.68 min; P<.001), but device setup time was markedly shorter (3.67, IQR 2.90-4.63 vs 9.85, IQR 8.03-11.35 min; P<.001). The experimental group achieved higher median device operation competency scores (90.00, IQR 80.00-100.00 vs 70.00, IQR 50.00-75.00 of 100; P<.001), passed more of the 22 evaluation steps (20.00, IQR 20.00-22.00 vs 16.00, IQR 13.00-18.00; P<.001), and required fewer assistance requests (0.00, IQR 0.00-1.00 vs 2.00, IQR 2.00-3.00; P<.001). Self-efficacy (20.00, IQR 18.00-25.00 vs 16.50, IQR 13.00-20.00; P=.003) and educational satisfaction (18.00, IQR 16.00-18.00 vs 12.00, IQR 9.75-15.00; P<.001) were also significantly higher in the experimental group. Effect sizes for the principal competency outcomes were large (Cohen d=1.2-3.1). AR-based training significantly improved emergency nurses' clinical competency, self-efficacy, and educational satisfaction in operating the Level-1 rapid infusion system compared with traditional self-directed learning. Despite requiring longer initial learning time, AR training produced faster device setup, greater accuracy, and enhanced learner independence. These findings suggest that AR technology can serve as an effective and scalable training solution for infrequently used but critically important medical devices in emergency care settings.

The persistent gap between hemostasis and tissue repair in wound care demands new biomaterials. To address this, we engineered an electrospun polysaccharide-based multilayer composite nanofiber membrane (MCNM) designed to transform early blood clots into bioactive, pro-regenerative interfaces. The MCNM integrates distinct carbohydrate polymer functionalities: a wound-contacting layer of pullulan/tannic acid/tranexamic acid nanofibers for hemostasis and fibrinolysis suppression; a polydopamine/CaCl2-modified cellulose acetate intermediate layer for platelet adhesion and fibrin nucleation; and a chitosan-composited cellulose spunlace backing for directional exudate management. When applied, this structure quickly concentrates blood to create a stable clot that acts as both hemostatic barrier and reservoir or regenerative factors. Proteomic analysis confirmed significant upregulation of extracellular matrix organization, focal adhesion, and actin cytoskeleton remodeling pathways within the clot microenvironment. In vivo, the MCNM accelerated wound closure, improved re-epithelialization and collagen deposition, and promoted anti-inflammatory macrophage polarization. This work establishes an example for leveraging polysaccharide-driven clot bioengineering to seamlessly bridge hemostasis and tissue regeneration in advanced wound care.

Medical futility in the cardiovascular care of older adults presents unique challenges that necessitate a nuanced understanding of both clinical and ethical dimensions. This state-of-the-art review explores the evolving concept of futility in the context of an ageing patient population and expanding armamentarium purported to treat even the most dire of cardiovascular diseases. The first objective is to delineate a framework for clinicians to elicit the different dimensions of futility, their relative importance to the patient, and their potential for improvement with the intervention being considered. Definitions are elaborated for quantitative futility-interventions with statistically negligible benefits-and qualitative futility-interventions misaligned with patient-specific goals and values. The second objective is to highlight the determinants of prohibitive risk, from the cardiovascular disease and procedural morbidity, to competing non-cardiovascular risks and frailty. A distinction is made between frailty and futility, and manifestations of severe frailty are reviewed based on the A-B-C-D-E mnemonic. The third and final objective is to discuss strategies and actionable approaches to care for patients once futility has been invoked. In addition to ongoing compassionate dialogue with the patient and family members, early initiation and aggressive pursuit of palliative care measures is beneficial for symptom control and quality of life. Ultimately, informed shared decision-making with a patient-centered philosophy is essential to uphold dignity and enhance the quality of life for older adults facing complex cardiovascular conditions.

The rapid expansion of immuno-oncology (I-O) and other advanced therapies is reshaping the complexity of early-phase clinical development. While core Phase I principles remain fundamental across oncology, emerging modalities introduce additional requirements for translational integration, specialized safety management, and therapeutic-specific infrastructure. However, the organizational functions of Phase I units have not evolved at the same pace and remain largely centered on conventional operational responsibilities. Drawing on the practices of leading Phase I units across the USA, Europe, and China, and comparing evolving regulatory frameworks of the US Food and Drug Administration, European Medicines Agency/Medicines and Healthcare products Regulatory Agency, and China's National Medical Products Administration, we propose a global perspective on the future development of Phase I units. We present a three-layer framework encompassing core Phase I foundations applicable across oncology, advanced translational capabilities, and ecosystem-level functions supporting emerging therapeutic development. Beyond ensuring patient safety and high-quality trial conduct, modern Phase I units should integrate translational research, artificial intelligence-enabled and model-informed drug development, regulatory science, and public engagement, while specialized centers may additionally support advanced therapy infrastructure, such as point-of-care manufacturing. Recognizing the diversity of institutional resources, we further propose a collaborative network model to facilitate scalable implementation and international harmonization. This framework positions Phase I units as integrated platforms connecting clinical investigation, translational science, regulatory innovation, and emerging therapy development, providing practical guidance for building future-ready early-phase clinical research infrastructure worldwide.

Nonmyeloablative-related haploidentical allogeneic stem cell transplantation (NMAC-HID allo-HSCT) has emerged as an additional treatment to achieve durable remission in sickle cell disease (SCD), a prevalent blood disorder characterized by painful vaso-occlusive crises and chronic anemia. The standard of care (SOC) for SCD includes hydroxyurea, pain management, and blood transfusion, but patients with SCD still lose several decades of life expectancy. Gene therapy (GT) for SCD is the other treatment for lifelong disease amelioration in SCD, with accessibility limited by cost and manufacturing capacity in the United States and globally. Two recent prospective studies that evaluated NMAC-HID allo-HSCT validated haploidentical allotransplantation as an efficacious and accessible treatment option in the era of GT. Given the ongoing price negotiation across jurisdictions for GT implementation and the absence of cost-effectiveness data comparing NMAC-HID allo-HSCT and GT, we conducted a cost-effectiveness analysis of NMAC-HID allo-HSCT vs GT vs SOC for adults and children living with SCD. The primary outcomes were the incremental cost-effectiveness ratio and the net monetary benefits across these 3 strategies. The secondary outcome was the maximum cost-effective threshold price for GT compared with NMAC-HID allo-HSCT. Treatment with SOC, NMAC-HID allo-HSCT, and GT accrued 14.3, 20.1, and 22.1 quality-adjusted life-years at costs of $1.22 million, $1.15 million, and $2.75 million, respectively. NMAC-HID allo-HSCT was the cost-effective strategy compared with GT in 100% of 10 000 Monte Carlo iterations across the base case and all scenario analyses. The maximum cost-effective thresholds for GT vs SOC were $1.4 million in the United States and $4200 to $22 000 across India, Nigeria, and Tanzania, depending on willingness-to-pay thresholds.