Seasonal influenza vaccination remains the most effective strategy for reducing influenza burden and preventing severe disease. Despite decades of vaccine development, the seasonal influenza vaccine is administered intramuscularly and provides suboptimal and highly variable effectiveness depending on host factors, pre-existing immunity, and antigenic match between vaccine and circulating strains. Recent advances in vaccine development have highlighted the potential of intranasal vaccine delivery as a strategy to increase protection against influenza virus infection by inducing local and systemic immune responses. Across multiple intranasal platforms under development, mucosal immunity, particularly secretory IgA and T- and B-cell immune responses, plays a central role in shaping protection against influenza virus infection. Live-attenuated influenza vaccines (LAIV) elicit protective immune responses, particularly in the pediatric population, and remain the only currently licensed intranasal seasonal influenza vaccine. However, variable performance in adults, strain-dependent viral fitness, and clinical contraindications have limited their broader applicability. These limitations have driven the development of next-generation intranasal influenza vaccine platforms designed to preserve the immunological advantages of mucosal vaccination while improving consistency, safety, and applicability across diverse populations. This review synthesizes current knowledge on licensed and emerging intranasal influenza vaccine platforms, including replicating viral platforms and non-replicating platforms, and discusses key immunological mechanisms, challenges, and translational progress. Together, these advances underscore the growing potential of intranasal vaccination as a next-generation strategy to improve influenza control.

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide, and Bacillus Calmette-Guérin (BCG) offers inconsistent protection against adult pulmonary TB. We previously showed that homologous mRNA vaccination encoding the mycobacterial antigen PPE15 (mRNA.PPE15) enhanced immunogenicity but did not improve protection over BCG alone. We hypothesised that a heterologous "prime-pull" strategy, systemic mRNA priming followed by mucosal adenoviral boosting, would enrich lung-resident memory T cells (TRM) and improve efficacy.

Female C57BL/6 mice received BCG prime followed by subunit regimens combining intramuscular mRNA.PPE15 and intranasal ChAdOx1.PPE15 in different administration orders, alongside homologous controls. Cellular responses in spleen and lung were quantified by intracellular cytokine staining after PPE15 peptides stimulation. Intravascular staining was used to distinguish parenchymal (IV-) from vascular (IV+) cells and combined with tetramer staining to identify PPE15-specific CD4+ and CD8+ TRM-phenotype in the lung parenchymal following vaccination. PPE15-specific serum antibodies were measured by ELISA. Protective efficacy was assessed four weeks after aerosol Mycobacterium tuberculosis (M.tb) challenge by lung and spleen CFU enumeration.

Heterologous vaccination induced robust spleen CD4+ and CD8+ responses and PPE15-specific IgG. In the lung, mRNA.PPE15-ChAdOx1.PPE15 induced IFN-γ+ CD4+ and CD8+ T cells in the parenchyma and PPE15-specific TRM-like cells. Following M.tb challenge, both heterologous regimens reduced lung CFU compared to naïve controls, but only mRNA.PPE15-ChAdOx1.PPE15 significantly decreased CFU in both lungs and spleen. When used to boost BCG, BCG-mRNA.PPE15-ChAdOx1.PPE15 achieved 0.8 log10 CFU reductions in lungs and spleen compared to BCG control group and induced the greatest numbers of lung TRM-phenotype cells.

A heterologous prime-pull strategy that combines intramuscular mRNA.PPE15 priming with intranasal ChAdOx1.PPE15 boosting effectively directs PPE15-specific T cells to the lung parenchyma, enriches TRM-like populations, and improves protection over homologous regimens. There was a trend for the mRNA.PPE15-ChAdOx1.PPE15 regimen to outperform the reverse order, particularly as a BCG booster. These data support heterologous platform vaccination and prime-pull strategy as a novel strategy for TB vaccines and indicate potential to progress to the next stages of vaccine development.

IntroductionPersistent asystole following restoration of mechanical circulation during extracorporeal cardiopulmonary resuscitation (E-CPR) is typically considered fatal. However, in profound hypothermia, electrical silence may not reflect irreversible myocardial injury.Case ReportA term neonate with severe meconium aspiration syndrome (MAS) was initially supported on veno-arterial ECMO at a regional hospital and transported to a tertiary ECMO facility. Following decannulation, she suffered cardiac arrest. Mechanical circulation was achieved after prolonged E-CPR with central cannulation, but the patient remained asystolic in the context of profound hypothermia (31.2°C). Electrical activity reappeared only after controlled rewarming to 33°C. She was discharged home on day 35 with a good long term neurological outcome.DiscussionNeonates are particularly prone to rapid hypothermia during resuscitation. Controlled rewarming is essential to determine cardiac viability before establishing futility.ConclusionUnder profound hypothermia, asystole after restoration of mechanical circulation does not preclude irreversible myocardial damage. Cautious rewarming is mandatory to assess myocardial prognosis.

Paradoxical coronary embolism (PCE) is an uncommon cause of acute myocardial infarction (AMI), typically occurring when venous thromboemboli cross a right-to-left shunt in the setting of elevated right-sided pressures. We report a case of mixed obstructive and cardiogenic shock caused by simultaneous pulmonary embolism (PE) and PCE. A previously healthy 43-year-old woman developed profound hypoxemia and inferior ST-segment elevation 3 days after knee surgery. Coronary angiography revealed distal right coronary artery occlusion, successfully treated with aspiration thrombectomy and percutaneous coronary intervention. Persistent hypoxemia, right ventricular injury, and hemodynamic collapse prompted initiation of venoarterial extracorporeal membrane oxygenation (VA ECMO). Subsequent imaging identified extensive bilateral PE and a patent foramen ovale with significant right-to-left shunting. Catheter-based pulmonary embolectomy improved cardiopulmonary function, followed by percutaneous PFO closure. She recovered fully and was discharged home neurologically intact. This case highlights the importance of early recognition, appropriate ECMO configuration, and comprehensive management of PCE with concurrent PE.

IntroductionExtracorporeal membrane oxygenation (ECMO) provides lifesaving support for severe respiratory and cardiac failure. Hybrid modes such as venoarteriopulmonary (VAP) may be necessary when conventional modes fail to meet complex physiological demands.Case ReportA 31-year-old woman with dermatomyositis-associated interstitial lung disease developed severe respiratory failure. She was initiated on venovenous (VV) ECMO, later complicated by right ventricular injury (RVI) requiring conversion to venopulmonary (VP) ECMO, and ultimately required hybrid VAP ECMO for progressive RVI and cardiogenic shock while awaiting heart-lung transplantation. The unique cannulation configuration provided additional cardiorespiratory support and hemodynamic stabilization, which later enabled safe transfer for transplantation.DiscussionHybrid VAP ECMO may provide effective rescue support for patients with refractory RVI and respiratory failure despite VP ECMO, preserve a surgically naïve chest, avoid differential oxygenation, and serve as a bridge to combined heart-lung transplant.ConclusionHybrid VAP ECMO represents an effective salvage strategy and bridge-to-transplant in complex cardiopulmonary failure.

While venous thromboembolism (VTE) is increasingly recognized in neonates and prothrombotic risk factors are being identified, no risk assessment model currently exists to enable early identification of neonates at high risk of VTE. A thorough understanding of existing evidence is necessary to inform the development of a risk-assessment model.

To describe maternal, obstetrical, and neonatal risk factors associated with VTE in neonates.

A literature search of Medline, Embase, CINAHL, and clinicaltrials.gov databases was performed on March 16, 2025, for peer-reviewed publications (1990-2025). Reference lists of included articles were screened to identify other potentially relevant publications.

Peer-reviewed studies describing factors associated with venous thrombosis in neonates up to 44 weeks of corrected gestational age were included. A total of 282 reports were retrieved and assessed for eligibility.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology reporting guidelines were used to guide data abstraction. Studies were screened independently by 4 trained investigators. Data were pooled using a random-effects model.

The primary outcome was the factors associated with venous thrombosis. Maternal and obstetrical and patient-related risk factors were considered; catheter-related risk factors are reported separately. Results are expressed using mean differences (MDs) or odds ratio (ORs) with 95% CIs. The degree of heterogeneity (ie, τ2) was estimated using the restricted maximum-likelihood model estimator. Risk of bias in included studies was assessed using the Risk of Bias in Non-randomised Studies of Interventions tool.

A total of 60 studies (3 366 507 neonates) were included; most were retrospective cohort studies (26 studies [43%]) or case-control studies (15 studies [25%]). The following risk factors were significantly associated with venous thrombosis: preeclampsia (OR, 2.66; 95% CI, 1.70-4.16; P < .001; τ2 = 0.00), low birth weight (OR, 2.05; 95% CI, 1.41-3.00; P < .001; τ2 = 0.00), cardiac disease (OR, 5.90; 95% CI, 1.16-30.05; P = .03; τ2 = 1.27), and infection (OR, 2.90; 95% CI, 1.88-4.48; P < .001; τ2 = 0.33). Several other factors were identified in multiple studies, but with inconsistent results, including maternal diabetes, gestational age and prematurity, asphyxia, mechanical ventilation, surgery, and elevated hemoglobin or hematocrit levels.

In this systematic review and meta-analysis, preeclampsia, low birth weight, cardiac disease, and infection were identified as risk factors of neonatal venous thrombosis. Heterogeneity between studies, lack of thrombosis outcome definition, and limited studies addressing common conditions and medications were identified, highlighting the need for further studies and risk stratification.

Conventional coronary computed tomography angiography (CCTA) lumen assessment is hampered by the similar attenuation of iodine and calcium. We assessed the lumen for Gd-enhanced CCTA on high-resolution color Gd K-edge imaging using a clinical spectral photon-counting computed tomography (SPCCT) prototype in an anthropomorphic phantom.

A hollow cylindrical coronary artery phantom (10-mm outer diameter, 5-mm inner diameter) containing five cylindrical calcifications of different densities (75, 100, 200, 400, and 800 mg/cm³ hydroxyapatite, deemed very low, low, medium, high, and very high, respectively) and equal size was scanned on a clinical SPCCT prototype using a clinical CCTA protocol. The artery model was filled with Gd mixed with saline to achieve 400 HU at 70 keV. The luminal area was compared with the physical area (i.e., 19.6 mm²), and spectral results were compared to conventional acquisition.

In the absence of calcification, physical lumen size was overestimated by 7% and 16% on color Gd K-edge and conventional images, respectively. In the presence of calcification, only color Gd K-edge images enabled the measurement of the lumen, i.e., 22.25 ± 0.43 mm², 22.85 ± 1.77 mm², 14.63 ± 1.17 mm², and 15.37 ± 0.78 for very low to very high calcium density, respectively. Largest underestimation (-26%) and overestimation (16%) were shown for the high- and low-density calcification in comparison to physical size, respectively.

Color Gd K-edge imaging with Gd-enhanced CCTA outperformed conventional imaging in assessing the coronary lumen in both noncalcified and calcified vessels, whilst accuracy depends on the presence and density of calcifications.

In a phantom study, high-resolution color Gd K-edge imaging targeting Gd enabled accurate visualization of the coronary lumen in both calcified and noncalcified arteries, outperforming conventional CT angiography. In the presence of calcifications, only color Gd K-edge imaging provided objective lumen assessment, with accuracy influenced by calcium extent and density.

Color Gd K-edge Gd-enhanced CCTA using SPCCT is feasible in a coronary artery phantom. Color Gd K-edge imaging improves lumen assessment in calcified vessels. Color Gd K-edge imaging potentially enhances diagnostic precision and treatment planning for patients with coronary artery disease.

Intravenous immunoglobulin (IVIg) is the standard of care for the treatment of Kawasaki disease (KD) and should be administered within 10 days of the onset of fever. Management guidelines for children with KD who defervesce spontaneously are not clear. In this study, we analysed patients with KD diagnosed between 1994 and 2024 at our centre who had defervesced spontaneously, had normal acute-phase reactants, and underwent echocardiographic examination, and in whom IVIg had not been administered. We reviewed the records of patients with KD from January 1994 - December 2024. The diagnosis of KD was based on standard guidelines. Patients with KD were said to be in spontaneous defervescence when they remained afebrile for ≥ 48 h, had normal acute-phase reactants [C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR)] and no coronary artery abnormalities (CAAs) on echocardiography at presentation, and when IVIg was not administered. Patients with spontaneous defervescence were subdivided into (i) early defervescence (Ed-KD), if the interval between onset of symptoms and defervescence was < 10 days, and (ii) late defervescence (Ld-KD), if the duration between onset of symptoms and defervescence was ≥ 10 days, respectively. Details of the clinical profile, laboratory investigations, and echocardiography findings were obtained from the records. Of the 1499 patients with KD enrolled during the study period, 115 patients (7.7%; 86 boys) defervesced spontaneously. The median age at disease onset was 6 years (mean, 5.6 years; range, 0.8-15 years). The median duration of fever, defined as the total duration of the febrile episode before spontaneous defervescence, was 5 days (range, 1-21 days). The median interval between illness onset (defined as fever onset) and diagnosis of KD was 15 days (range, 4-40 days), indicating that diagnosis was often made after fever had already subsided. The most common clinical feature was periungual desquamation, followed by rash, oral-mucosal changes, cervical lymphadenopathy, and conjunctival injection. Incomplete presentation was noted in 73.9% (n = 85/115) of patients. No patient has developed CAAs or other cardiac sequelae over a median follow-up of 9 months (range 2 months-156 months). The cumulative follow-up for the cohort was 235 patient-years. The 'low-risk' subgroup of patients with KD who defervesce spontaneously, and have normal acute phase reactants with no CAAs at presentation, have good clinical and coronary outcomes.

More children are undergoing congenital or non-congenital cardiac surgery today which can impact outcomes for subsequent thoracic surgery. However, post-lung transplant (LTx) outcomes of children with previous cardiac surgery are unknown, so we explored this important issue using a publicly available database.

A retrospective analysis was performed using the Scientific Registry of Transplant Recipients (SRTR). First-time pediatric LTx candidates without and with history of prior cardiac surgery, excluding previous cardiothoracic transplantation, from 2003 to 2024 were enrolled into our study. Univariate analyses, multivariable Cox regression, and Kaplan-Meier plots were performed for a comprehensive analysis.

We identified 1333 and 144 LTx candidates without and with prior cardiac surgery (52 with congenital surgery, 92 with non-congenital surgery) with more children with cardiac surgery being listed for LTx over time. There were 811 LTx recipients without prior cardiac surgery compared to 63 with prior cardiac surgery (14 congenital, 49 non-congenital). Children with prior congenital cardiac surgery were much younger, and pulmonary vascular disease (PVD) was the most common indication for LTx. Prior non-congenital cardiac surgery did not negatively impact short- or long-term post-LTx outcomes in children. However, history of congenital cardiac surgery was associated with high waitlist mortality (31% compared to 15% (no surgery) and 21% (non-congenital surgery), p < 0.001) and worse long-term outcomes (HR 1.89; 95% CI 1.01, 3.53, p = 0.048).

There is an increasing number of children with previous cardiac surgery undergoing LTx especially in the setting of congenital heart disease with subsequent PVD.

Elevated low-density lipoprotein cholesterol (LDL-C) leads to atherosclerotic plaque buildup and drives cardiovascular disease. Despite the availability of effective therapies for LDL-C reduction, elevated LDL-C is common in the United States.

To measure the success of a pharmacist-led telephonic outreach program designed to proactively address individuals with hyperlipidemia who were not being treated in accordance with cholesterol guidelines and collaborate with their primary care clinicians (PCCs) to increase guideline-based care.

The 3-month outreach occurred from September through November 2023. Health plan members with 1 inpatient or 2 outpatient claims for hyperlipidemia within the previous year were determined using International Classification of Diseases, Tenth Revision, Clinical Modification codes. Members not managed in accordance with the 2018 American Heart Association/American College of Cardiology (ACC)/Multisociety Guideline and 2022 ACC Expert Consensus Decision Pathway, based on available claims data, received a personalized action recommendation. The outreach team contacted the member and scheduled a phone call with a pharmacist. If the member agreed to the pharmacist's clinical recommendation, the outreach team contacted the member's PCC directly (by fax or e-mail). PCCs were responsible for the final clinical decision and action.

Of 14,979 members who met the inclusion criteria, 883 were selected at random for contact by the outreach team. Of these, 667 members (76%) accepted a call with a pharmacist and were considered the intervention group. An additional 5,266 members who were not contacted and did not share a PCC with someone in the intervention group were included as the control group. In the intervention group, 92.4% of members accepted the guideline-based hyperlipidemia recommendation, allowing the pharmacist to contact their PCC. The overall percentage of members moving toward guideline-recommended care in the intervention group (25.5%) was approximately twice that in the control group (11.1%). Members could undergo an LDL-C test if they had no LDL-C result available, initiated lipid-lowering therapy (LLT) if they were not already being treated for hypercholesterolemia, or intensified their existing statin regimen or added a nonstatin LLT. The difference in proportion of members remaining on no statin throughout the program was significantly lower in the intervention group (-7.9% [95% CI = -11.3% to -4.5%]) vs the control group. At the end of the pilot, 8.7% (58 of 667) of intervention group members received LLT in accordance with current guidelines vs 6.0% (316 of 5,266) in the control group.

This study demonstrated that a health plan-driven, pharmacist-led, educational outreach program increased movement toward guideline-based LDL-C management in a 3-month pilot. Similar programs could increase the proportion of members receiving guideline-based care in a variety of chronic disease settings.