Bispecific antibodies(BsAbs) are a novel class of therapy for relapsed/refractory multiple myeloma (RRMM), leading to deep and durable responses in heavily pretreated patients. Their use is associated with a high burden of infections, particularly with anti-BCMA-targeting agents. This retrospective, single-center study included 50 RRMM patients treated with anti-BCMA or anti-GPRC5D BsAbs, of whom 13 received both agents because of disease progression. Standard prophylactic strategies included vaccination, antimicrobial prophylaxis, and, in selected patients, subcutaneous immunoglobulin (SCIg). Overall, 78% of patients received prior vaccinations and those with ≥3-4 vaccines exhibited the lowest infection-related mortality (23.4%, respectively 6.7%). We analyzed 121 infectious episodes recorded during the study period, of which 45.5% were severe (grade ≥3). The respiratory tract was the most affected site (65%), by viral (43%) and bacterial (45%) etiologies. Anti-BCMA BsAb were associated with a higher incidence and severity of infections, as well as a shorter median time to first infection compared with anti-GPRC5D therapy (2.3 vs 3.8 months). Infectious complications occurred throughout the course of therapy, with the highest risk observed early after treatment initiation, while remaining clinically relevant during prolonged follow-up. Infection-related mortality was the second leading cause of death (34%), after disease progression. Multivariable analyses showed that male sex and patients with high-risk disease were associated with increased infection risk.

Post-acute sequelae of SARS-CoV-2 (PASC) or Long-COVID affects millions and remains mechanistically undefined due to its heterogeneous clinical presentation. Identifying robust biological signatures is essential for understanding disease mechanisms and improving diagnosis. Here, we investigated the protein cargo of plasma-derived small extracellular vesicles (SEVs) from PASC-positive and PASC-negative individuals to identify EV-linked biomarkers of Long-COVID.

SEVs were isolated from EDTA plasma of PASC-positive (n=20) and PASC-negative (n=11) individuals using size-exclusion chromatography. SEV protein cargo was profiled across more than 5400 proteins using the Olink Explore HT platform.

PASC-positive patients commonly reported fatigue, shortness of breath, brain fog, sleep disruption, and mood changes. Proteomic analysis revealed 269 significantly dysregulated proteins, including 84 upregulated and 21 downregulated, with a fold change >2 in PASC. These differentially altered proteins were enriched in pathways related to coagulation, inflammation, apoptosis, fibrosis, extracellular matrix remodeling, mitochondrial dynamics, and immune activation. PASC-positive SEVs showed persistent increases in FN1, HCF-H, HGF, and IL-17RA, proteins previously dysregulated in acute COVID-19. These markers showed greater differences in SEVs than in matched plasma, particularly HGF and IL-17RA, which were significantly altered in SEVs but not in plasma.

Proteomic alterations in SEVs from PASC patients highlight the inflammatory, thrombotic, and neurobiological dysregulation, underscoring the potential of SEVs as biomarkers and mechanistic drivers of long COVID.

Pulmonary arterial hypertension (PAH) is a progressive disease characterised by vascular remodelling. Inflammatory responses and oxidative stress have been shown to contribute to its progression. This study investigated the effects of a novel HIF-1α-miR-663b axis on pulmonary arterial smooth muscle inflammation, oxidative stress and apoptosis in a monocrotaline (MCT)-induced PAH rat model. A PAH rat model was constructed via MCT injection; moreover, miR-663b inhibitors were administered to inhibit miR-663b. PASMCs were cultured under hypoxic conditions to establish an in vitro PAH model. The data revealed that miR-663b was highly expressed in PAH rats and hypoxia-induced PASMC models. Overexpression of miR-663b exacerbated hypoxia-induced proliferation, apoptosis, migration and inflammation in PASMCs. Conversely, miR-663b inhibition reversed hypoxia-induced dysfunction in PASMCs. ZBP1 downregulation dampened miR-663b upregulation-mediated dysfunctions in PASMCs. In vivo experiments revealed that miR-663b inhibitors mitigated pulmonary arterial remodelling, inflammation and PANoptosis in MCT-induced PAH rats. HIF-1α expression was upregulated in hypoxia-induced PASMCs. ChIP-qPCR and dual-luciferase reporter gene assays confirmed that HIF-1α transcriptionally regulated and promoted miR-663b expression. Upregulation of miR-663b inhibited AMPK/Sirt1 signalling pathway activation and promoted ZBP1-mediated PANoptosis. However, miR-663b inhibitors reversed hypoxia-induced PANoptosis in PASMCs. The protective effects of miR-663b inhibitors on PASMCs and their inhibitory effects on PANoptosis were significantly weakened by treatment with an AMPK inhibitor or a Sirt1 inhibitor. Collectively, these findings suggest that inhibiting HIF-1α-mediated miR-663b expression improves PAH by reducing PASMC dysfunction through the attenuation of inflammatory responses, oxidative stress and apoptosis in PASMCs and the activation of the AMPK/Sirt1 pathway.

Choosing between endovascular and open (bypass) surgical revascularization for chronic limb-threatening ischemia has major implications for clinical practice.

To evaluate the cost-effectiveness of endovascular vs bypass surgical revascularization.

This economic evaluation used individual-level data from the Best Endovascular vs Best Surgical Therapy for Patients With Chronic Limb Ischemia (BEST-CLI) trial, with the first patient enrolled August 28, 2014, and the final October 18, 2019, for a median follow-up of 2.7 years. An individual-level, continuous-time Markov model with health states based on adjudicated clinical events from BEST-CLI was developed. Rates of clinical outcomes, health utilities, and health care resource use were derived from trial data. Unit costs came from Medicare insurance claims data and the physician fee schedule. The data were analyzed between June 27, 2025, and May 28, 2026.

The main outcomes were incremental cost per life-years gained, incremental quality-adjusted life-years (QALYs) gained, incremental net monetary benefit, and cost per major events of revascularization and amputation avoided over a 5- and 10-year time horizon. One-way and probabilistic sensitivity analyses were performed to quantify uncertainty.

The cohort included 1434 patients from BEST-CLI (mean [SD] age, 67 [10] years; 1026 male [71.5%]). In the base case analysis, over a 5-year time horizon, the mean per-person direct medical costs were $118 559 (95% credible interval [CrI], $86 978-$157 152) for bypass surgery and $125 535 (95% CrI, $96 205-$160 357) for endovascular surgery. The mean survival per person was 3.84 years (95% CrI, 3.74-3.93 years) and 3.78 years (95% CrI, 3.61-3.94 years) for bypass and endovascular surgery, respectively. The mean QALYs per person were 2.53 (95% CrI, 2.34-2.70) for bypass surgery and 2.48 (95% CrI, 2.28-2.67) for endovascular surgery. Bypass surgery dominated endovascular surgery with respect to both costs per life-year and per QALY gained. The results over 10 years were consistent with those of the 5-year BEST-CLI follow-up. In the Monte Carlo simulation, there was a 93% chance that bypass surgery was more cost-effective than endovascular surgery.

This cost-effectiveness study found that bypass surgery was more cost-effective in most probabilistic simulations; however, uncertainty remained, highlighting the need for future research to identify subgroups in whom each approach may be cost-effective.

Heart failure (HF) represents a major burden on healthcare systems globally, driven by high rates of hospitalizations and readmissions, as well as prolonged length of stay (LOS). To address this, a wide range of innovative strategies have emerged and evolved in recent years. These approaches span a broad spectrum, ranging from novel routes of medication administration to digital health technologies such as telemonitoring, wearable devices, as well as implantable devices. Given the rapid expansion of available innovations, it can be challenging for clinicians to remain fully up to date with emerging tools and evidence. At the 2026 ESC Heart Failure Congress in Barcelona, Spain, global experts in the field highlighted different technologies and the key clinical trials supporting them. This review aims to synthesize the most recent innovative strategies aimed at reducing HF hospitalizations (HFH), as presented during the congress.

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition with high morbidity and mortality. Long-term outcomes remain difficult to predict. Computed tomography (CT) is central to diagnosis and early risk stratification, yet the prognostic value of non-contrast CT at the end of the acute care phase is not fully established. We conducted a retrospective single-center study of adult patients with confirmed aSAH admitted to the Neurocritical Care Unit (NCCU) of the University Hospital Zurich (January 2016-June 2024). Survivors with CT at discharge from the NCCU and 12-month follow-up were included. Functional outcome was assessed using the Glasgow Outcome Scale Extended (GOSE) and dichotomized as favorable (5-8) or unfavorable (1-4). CT scans were evaluated for infarcts, hemorrhage distribution, hydrocephalus requiring shunt, midline shift, and decompressive surgery. Multivariable logistic regression with multiple imputation by chained equations (MICE) addressed missing data, with days from admission to discharge CT included as a covariate in the clinical-severity model to control for differential timing. Discriminative performance was assessed using receiver operating characteristic (ROC) curve analysis. Of 500 admitted patients, 325 met inclusion criteria. At 12 months, 234 had favorable and 91 unfavorable outcomes. In a radiological model, increasing age and infarcts involving the thalamus, basal ganglia, corpus callosum, and cerebellum, together with cortical infarction and intraventricular hemorrhage, were independently associated with unfavorable outcome; sulcal subarachnoid hemorrhage showed only a non-significant trend toward a protective association. In a separate clinical-severity model, increasing age, ventriculoperitoneal shunt placement, decompressive craniectomy, and days-to-CT scan were independently associated with unfavorable outcome. ROC analysis showed low-to-moderate discriminative ability (AUC range 0.529-0.688), with intraventricular hemorrhage performing best. Discharge non-contrast CT provides incremental prognostic information in aSAH survivors. Deep or midline infarctions are particularly decisive for early prognostication and rehabilitation using routinely available imaging.

Objective to evaluate whether withholding prophylactic antiseizure medications (ASMs) is safe in low-risk patients undergoing microsurgical clipping for unruptured intracranial aneurysms (UIAs) and to identify risk factors of postoperative seizures using a prespecified noninferiority design. Methods this prospective single-center cohort study enrolled adults between January 2019 and June 2023 who were scheduled to undergo clipping for UIAs smaller than 15 mm and had no prior seizures or structural brain injury. Prophylactic ASMs were not administered. The primary endpoint was postoperative seizure within 1 year. Noninferiority was assessed using an exact binomial framework against a prespecified margin of 5.5%. Predictors were evaluated using univariable and multivariable Firth penalized logistic regression. Internal validation was performed with 1,000 bootstrap resamples. Results among 428 patients, postoperative seizures occurred in 7 patients (1.6%). The exact two-sided 95% confidence interval for seizure incidence was 0.66% to 3.34%, and the upper bound remained below the prespecified noninferiority margin of 5.5%. A one-sided exact binomial test confirmed that the seizure rate was significantly below the noninferiority threshold (p < 0.001). Five seizures occurred within 48 h of surgery, and two occurred on postoperative days 25 and 120. In multivariable Firth regression, postoperative infarction showed the strongest association with seizures (adjusted OR 68.63, 95% CI 9.48-468.60), which was supported by bootstrap validation (median OR 72.53, 95% CI 9.32-726.52). dACA location showed a borderline association in the multivariable model (p = 0.085) but demonstrated a consistent positive association in bootstrap resampling (median OR 10.25, 95% CI 2.92-40.21). Conclusion in this prospective non-ASM cohort of low-risk patients undergoing UIA clipping, withholding prophylactic ASMs was noninferior with respect to postoperative seizure incidence, and most seizures were transient. Postoperative infarction showed the most prominent association with postoperative seizure, supporting a selective, risk-adapted strategy rather than routine prophylactic ASM use. Trial Registration clinical Research Information Service (CRIS), KCT0004461, registered on November 22, 2019.

The presence of abnormal nailfold capillaries and antinuclear antibodies (ANA) is associated with increased all-cause mortality in patients presenting with incipient Raynaud's phenomenon (RP). We conducted a retrospective analysis aiming to assess the association between abnormal nailfold capillaries, ANA, and mortality over a 20-year follow-up period. In 2958 patients with incipient RP without previously known connective tissue disease, nailfold capillaroscopies and laboratory tests for ANA and ANA-subsets were obtained. Of these, long-term follow-up data were available for 2922 patients. Over a median follow-up period of 23 (IQR 20.2-25.2) years, 832 patients died, of which 562 were women (25% of female patients) and 270 were men (41% of male patients). Compared to a demographically matched reference population, mortality was increased in female and male patients with RP (log-rank test < 0.001). In female patients with RP, the presence of ANA, anti-Scl-70 antibodies, and a grouping variable consisting of giant capillaries, reduced capillary density, and avascular fields was associated with an increase in all-cause mortality. The highest mortality was observed in patients presenting both abnormal nailfold capillaries and ANA. In the long-term, an excess mortality persists in patients with RP. Our study demonstrates prognostic associations between abnormal nailfold capillaries as well as ANA and mortality.

Stroke can have a range of impacts on a person's life. Previous research has highlighted the need for greater attention to well-being, with people with stroke reporting that well-being is not well addressed in stroke services and therefore remains an area of unmet need. While previous research has considered how services address well-being, this study focused on those with stroke, exploring the work they did to maintain and enhance their well-being while receiving care from stroke services. It also examined how stroke services appeared to influence this work.

Underpinned by Interpretive Description methodology, interviews were conducted with 37 people impacted by stroke (24 people with stroke, 13 family members) across the North Island of Aotearoa New Zealand. Data were analysed using directed content analysis guided by Normalisation Process Theory.

People described undertaking significant work to support their well-being whilst receiving care from stroke services. We identified six interwoven forms of work which involved 'inward work'-sense-making, emotional work and reconnecting work-and 'outward work'-navigating health services, advocating for needs and doing rehabilitation. All were influenced by a person's network of relationships. People impacted by stroke perceived that the depth of this work was unseen by health professionals and described how stroke services could act to either reduce or exacerbate the work that they were doing for their well-being.

These findings show how people actively work to sustain their well-being whilst receiving care from stroke services. By examining how stroke services influence this 'well-being work', we highlight areas where health services may focus efforts to support well-being. Health professionals can acknowledge the work that people are doing and foster the resources they already hold, such as supporting people to engage in roles, relationships, cultural practices and social contexts that support their well-being from early in care. By doing so, health professionals and service leaders may set a foundation to better support people's well-being both in the moment and in the long-term.

People with stroke, family members, and people who provide support to people with stroke, and health professionals set priorities for this research. They advised on study conduct and have provided feedback on wider findings from the research.

Acute ischemic stroke is a leading cause of death and disability. Despite strong evidence supporting reperfusion therapies and Stroke Unit care, access and quality of stroke services remain heterogeneous across Europe. Although national stroke registries provide valuable real-world data, fragmentation, limited interoperability, and data protection constraints have restricted multinational analyses and benchmarking.

The Federating European REgistries for Stroke (FERES) initiative establishes a GDPR-compliant federated framework for secondary use of stroke registry data. FERES harmonizes heterogeneous datasets through a stroke-specific Common Data Elements (CDE) model and performs analyses locally within each registry using the Medical Informatics Platform, sharing only aggregated, non-identifiable outputs. To validate the framework, a predefined showcase analysis comparing anterior versus posterior circulation acute ischemic stroke was executed in both centralized and federated modes using an identical harmonized dataset.

FERES connected five national registries from Austria, Greece, Ireland, Italy, and Switzerland within a unified federated infrastructure. At the time of analysis, 149,772 patient events from two registries were accessible for federated querying, with three additional registries technically integrated and in advanced onboarding. The harmonized ontology comprised 945 standardized variables spanning the stroke care pathway. Federated execution reproduced centralized pooled-data results across descriptive statistics, hypothesis testing, effect sizes, and multivariable regression models with only minimal numerical discrepancies.

FERES demonstrates that large-scale, multinational stroke research and benchmarking can be conducted in Europe using a privacy-preserving federated approach, providing a scalable foundation for cross-border real-world evidence generation and quality improvement.