Impact of an early educational protocol on the oral language of children born preterm exhibiting phonological fragility: a multicenter randomized clinical trial.

Unlabelled: We conducted a six-center, prospective, randomized, open-label trial to assess whether an early standardized educational protocol provided from 42 to 48 months of age improved the progression of oral language and phonological development in children born preterm. A total of 552 children with phonological fragility were included in this study. The children were randomized to receive the educational protocol (guided arm,  = 87) or not (non-guided arm,  = 78).

Plasminogen Activator Inhibitor-1 in the Pathophysiology of Late Life Depression.

Introduction: Late life depression (LLD) is characterized by specific clinical features including a high frequency of vascular form and frequent antidepressant treatment resistance. The expression and functions of the serine protease inhibitor, Plasminogen Activator Inhibitor-1 (PAI-1) is known to be altered by aging, vascular damage, insulin levels associated with a sedentary lifestyle, chronic stress leading to hypercortisolemia, and inflammatory changes linked to stress responses. These phenomena would be implicated in LLD like vascular depression.

NIVO-TIL: combination anti-PD-1 therapy and adoptive T-cell transfer in untreated metastatic melanoma: an exploratory open-label phase I trial.

Background And Purpose: In patients with metastatic melanoma who respond to anti-PD-1 therapy, the proliferation of intra-tumour CD8+ T cells is directly correlated with the clinical response, making tumour-infiltrating lymphocytes (TILs) a treatment of interest in combination with a PD-1 inhibitor, which is the undisputed gold standard in the management of metastatic melanoma. The aim of this trial was, therefore, to evaluate the safety and efficacy of sequential combination therapy consisting of nivolumab (a PD-1 inhibitor) and TILs adoptive T cells in patients with metastatic melanoma.

Materials And Methods: We performed an exploratory, prospective, single-centre, open-label, non-randomised, uncontrolled phase I/II study.

Single-nucleus RNA sequencing reveals glial cell type-specific responses to ischemic stroke in male rodents.

Neuroglia critically shape the brain´s response to ischemic stroke. However, their phenotypic heterogeneity impedes a holistic understanding of the cellular composition of the early ischemic lesion. Here we present a single cell resolution transcriptomics dataset of the brain´s acute response to infarction.

Distinct Substrates of Idiopathic Ventricular Fibrillation Revealed by Arrhythmia Characteristics on Implantable Cardioverter-Defibrillator.

Background: Idiopathic ventricular fibrillation (IVF) can be associated with undetected distinct conditions such as microstructural cardiomyopathic alterations (MiCM) or Purkinje (Purk) activities with structurally normal hearts.

Objectives: This study sought to evaluate the characteristics of recurrent VF recorded on implantable defibrillator electrograms, associated with these substrates.

Methods: This was a multicenter collaboration study.

Central nervous system-associated macrophages modulate the immune response following stroke in aged mice.

Age is a major nonmodifiable risk factor for ischemic stroke. Central nervous system-associated macrophages (CAMs) are resident immune cells located along the brain vasculature at the interface between the blood circulation and the parenchyma. By using a clinically relevant thromboembolic stroke model in young and aged male mice and corresponding human tissue samples, we show that during aging, CAMs acquire a central role in orchestrating immune cell trafficking after stroke through the specific modulation of adhesion molecules by endothelial cells.

Long-term survival after anti-PD-1 discontinuation in advanced cutaneous squamous cell carcinoma (cSCC): a proof of concept of benefit of concomitant cemiplimab and radiotherapy.

Background: In a princeps study we conducted in patients with advanced cutaneous squamous cell carcinoma treated with concomitant anti-Programmed cell death protein 1 (PD-1) and radiotherapy, we demonstrated a clinico radiological response to cemiplimab that appeared to persist over time, 1 year after treatment discontinuation.

Method: We conducted a single-center descriptive study at Caen Hospital from September 1, 2021 to September 2023, in 14 patients with advanced carcinoma treated with cemiplimab until September 1, 2021. The aim of this update is to examine clinical and radiological follow-up 2 years after discontinuation of cemiplimab.

CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology.

Intracerebral aneurysms (IAs) are pathological dilatations of cerebral arteries whose rupture leads to subarachnoid hemorrhage, a significant cause of disability and death. Inflammation is recognized as a critical contributor to the formation, growth, and rupture of IAs; however, its precise actors have not yet been fully elucidated. Here, we report CNS-associated macrophages (CAMs), also known as border-associated macrophages, as one of the key players in IA pathogenesis, acting as critical mediators of inflammatory processes related to IA ruptures.

Modulation of Abundance and Location of High-Mobility Group Box 1 in Human Microglia and Macrophages under Oxygen-Glucose Deprivation.

While stroke represents one of the main causes of death worldwide, available effective drug treatment options remain limited to classic thrombolysis with recombinant tissue plasminogen activator (rtPA) for arterial-clot occlusion. Following stroke, multiple pathways become engaged in producing a vicious proinflammatory cycle through the release of damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB1) and heat shock protein 70 kDa (HSP72). HMGB1, in particular, can activate proinflammatory cytokine production when acetylated (AcHMGB1), a form that prefers cytosolic localization and extracellular release.

Pharmacological preclinical comparison of tenecteplase and alteplase for the treatment of acute stroke.

Alteplase (rtPA) remains the standard thrombolytic drug for acute ischemic stroke. However, new rtPA-derived molecules, such as tenecteplase (TNK), with prolonged half-lives following a single administration, have been developed. Although TNK is currently under clinical evaluation, the limited preclinical data highlight the need for additional studies to elucidate its benefits.

Leptomeningeal collaterals regulate reperfusion in ischemic stroke and rescue the brain from futile recanalization.

Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet-unknown functions.

The niche matters: origin, function and fate of CNS-associated macrophages during health and disease.

There are several cellular and acellular structural barriers associated with the brain interfaces, which include the dura, the leptomeninges, the perivascular space and the choroid plexus epithelium. Each structure is enriched by distinct myeloid populations, which mainly originate from erythromyeloid precursors (EMP) in the embryonic yolk sac and seed the CNS during embryogenesis. However, depending on the precise microanatomical environment, resident myeloid cells differ in their marker profile, turnover and the extent to which they can be replenished by blood-derived cells.

Parabiosis Discriminates the Circulating, Endothelial, and Parenchymal Contributions of Endogenous Tissue-Type Plasminogen Activator to Stroke.

Background: Intravenous injection of alteplase, a recombinant tPA (tissue-type plasminogen activator) as a thrombolytic agent has revolutionized ischemic stroke management. However, tPA is a more complex enzyme than expected, being for instance able to promote thrombolysis, but at the same time, also able to influence neuronal survival and to affect the integrity of the blood-brain barrier. Accordingly, the respective impact of endogenous tPA expressed/present in the brain parenchyma versus in the circulation during stroke remains debated.

Improving stroke outcomes in hyperglycemic mice by modulating tPA/NMDAR signaling to reduce inflammation and hemorrhages.

The pharmacological intervention for ischemic stroke hinges on intravenous administration of the recombinant tissue-type plasminogen activator (rtPA, Alteplase/Actilyse) either as a standalone treatment or in conjunction with thrombectomy. However, despite its clinical significance, broader use of rtPA is constrained because of the risk of hemorrhagic transformations (HTs). Furthermore, the presence of diabetes or chronic hyperglycemia is associated with an elevated risk of HT subsequent to thrombolysis.

Thrombolytic therapy based on lyophilized platelet-derived nanocarriers for ischemic stroke.

Background: Intravenous administration of fibrinolytic drugs, such as recombinant tissue plasminogen activator (rtPA) is the standard treatment of acute thrombotic diseases. However, current fibrinolytics exhibit limited clinical efficacy because of their short plasma half-lives and risk of hemorrhagic transformations. Platelet membrane-based nanocarriers have received increasing attention for ischemic stroke therapies, as they have natural thrombus-targeting activity, can prolong half-life of the fibrinolytic therapy, and reduce side effects.

rtPA-loaded fucoidan polymer microbubbles for the targeted treatment of stroke.

Systemic injection of thrombolytic drugs is the gold standard treatment for non-invasive blood clot resolution. The most serious risks associated with the intravenous injection of tissue plasminogen activator-like proteins are the bleeding complication and the dose related neurotoxicity. Indeed, the drug has to be injected in high concentrations due to its short half-life, the presence of its natural blood inhibitor (PAI-1) and the fast hepatic clearance (0.

A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia.

Although dementia research has been dominated by Alzheimer's disease (AD), most dementia in older people is now recognised to be due to mixed pathologies, usually combining vascular and AD brain pathology. Vascular cognitive impairment (VCI), which encompasses vascular dementia (VaD) is the second most common type of dementia. Models of VCI have been delayed by limited understanding of the underlying aetiology and pathogenesis.

Optical coherence tomography angiography findings in retinal cavernous hemangioma: New cases and review of the literature.

Introduction: Retinal cavernous hemangioma (RCH) is a rare retinal vascular disease characterized by grape-like clusters of saccular aneurysms, usually unilateral, asymptomatic and non-progressive. The diagnosis is made by multimodal imaging including conventional fluorescein angiography (FA). The recent introduction of swept source optical coherence tomography angiography (SS-OCTA) has allowed new insight into vascular diseases, allowing non-invasive, more precise visualization of retinal and choroidal blood flow, and represents a possible alternative to FA.

Cardiovascular Immunotoxicity Associated with Immune Checkpoint Inhibitors in Metastatic Melanoma.

Background: Checkpoint inhibitors, such as PD-1 inhibitors (nivolumab, pembrolizumab) and anti-CTLA-4 (CD152) (ipilimumab), are widely used in metastatic melanoma, and most immune-related adverse events are known. Several cardiovascular AEs (CVAEs) associated with immune checkpoint inhibitor exposure have been reported in post-marketing surveillance studies and represent major issues for patients with melanoma during and after cancer treatment. Data on CVAES induced by immune checkpoint inhibitors in melanoma, especially incidence and risk factors, are lacking.

Cutaneous manifestations induced by check point inhibitors in 120 melanoma patients-The European MelSkinTox study.

Background: Checkpoint inhibitors provide an effective approach for the melanoma treatment. They prolong lymphocyte effects, which explains the cytotoxicity underlying immune-related adverse events (IrAEs). Cutaneous IrAEs affect nearly 40% of PD-1i and 50% of CTLA4i-treated patients.