The Role of Atrial Fibrillation and Oral Anticoagulation Status in Health-Related Quality of Life 12 Months After Ischemic Stroke or TIA.

Aims: Atrial fibrillation (AF) accounts for about 20% of all ischemic strokes worldwide. It is known that AF impairs health-related quality of life (HRQOL) in the general population, but data on HRQOL in stroke patients with newly diagnosed AF are sparse.

Methods: Post hoc analysis of the prospective, investigator-initiated, multicenter MonDAFIS study (NCT02204267) to analyze whether AF-related oral anticoagulation (OAC), and/or AF-symptom severity are associated with HRQOL after ischemic stroke or transient ischemic attack (TIA).

The Importance of Bright Spotty Lesions on Magnetic Resonance Imaging in Predicting Chronic Neuropathic Pain in Myelitis.

: Chronic neuropathic pain (CNP) stands as one of the most debilitating complications in patients with myelitis owing to its challenging management. Bright spotty lesions (BSLs) are frequently observed in neuromyelitis optica spectrum disorder (NMOSD), but few reports have discussed CNP in myelitis. We aim to demonstrate that BSLs could be one of the potential prognostic factors for CNP development in myelitis.

Heparin Resistance in Patients Receiving Extracorporeal Membrane Oxygenation: A Review.

Heparin resistance (HR) in patients on extracorporeal membrane oxygenation (ECMO) exacerbates bleeding and thrombogenesis. Thus far, there is no universal definition of what this condition entails and no unified strategy for assessing heparin's efficacy in ECMO patients. The most frequent discrepancy when it comes to defining HR is the difference in the reported doses: units per day (U/d) or per kilogram per hour (U/kg/h).

Increased Antibiotic Susceptibility of Gram-Positive Bacteria in Cerebrospinal Fluid Compared to Broth.

In hospital- and community-acquired central nervous system infections, resistant Gram-positive bacteria are an increasing therapeutic challenge. The present approach does not attempt to identify rapidly bactericidal therapies for susceptible pathogens but aims to improve methods to find antibiotic regimens for multi-resistant pathogens that are effective in vivo in spite of reduced in vitro susceptibility in culture media. Antibiotic susceptibility was tested in cerebrospinal fluid (CSF) and Mueller-Hinton broth (, methicillin-resistant , ) or brain-heart infusion ().

Added Value of Biological Effective Dose in Dosiomics-Based Modelling of Late Rectal Bleeding in Prostate Cancer.

Background/objectives: Extracting spatial features (texture analysis) from dose distributions (dosiomics) for outcome prediction is a rapidly evolving field in radiotherapy. To account for fraction size differences, the biological effective dose (BED) is often calculated. We evaluated the impact and added value of the BED in the dosiomics prediction modelling of grade ≥ 2 late rectal bleeding (LRB) probability within 5 years after treatment in three parts.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Addressing inter individual variability in CSF levels of brain derived proteins across neurodegenerative diseases.

Accurate diagnosis and monitoring of neurodegenerative diseases require reliable biomarkers. Cerebrospinal fluid (CSF) proteins are promising candidates for reflecting brain pathology; however, their diagnostic utility may be compromised by natural variability between individuals, weakening their association with disease. Here, we measured the levels of 69 pre-selected proteins in cerebrospinal fluid using antibody-based suspension bead array technology in a multi-disease cohort of 499 individuals with neurodegenerative disorders including Alzheimer's disease (AD), behavioral variant frontotemporal dementia, primary progressive aphasias, amyotrophic lateral sclerosis (ALS), corticobasal syndrome, primary supranuclear palsy, along with healthy controls.

Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease.

This review demonstrates the value of central pharmacodynamics (PD), including positron emission tomography (PET) and computerized cognitive testing, to supplement pharmacokinetic (PK) and peripheral PD for determining the target dose range for clinical efficacy testing of emestedastat, an 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor. Combined data from 6 clinical trials in cognitively normal volunteers and patients with Alzheimer disease included a population PK model, endocrine PD, a human PET trial (11β-HSD1 brain imaging), and computerized cognitive testing. PK and PET findings were similar in volunteers and patients with Alzheimer disease.

Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathy.

Loss of Bcl2-associated athanogene 3 (BAG3) is associated with dilated cardiomyopathy (DCM). BAG3 regulates sarcomere protein turnover in cardiomyocytes; however, the function of BAG3 in other cardiac cell types is understudied. In this study, we used an isogenic pair of BAG3-knockout and wild-type human induced pluripotent stem cells (hiPSCs) to interrogate the role of BAG3 in hiPSC-derived cardiac fibroblasts (CFs).

Guidelines for the standardization of pre-analytical variables for salivary biomarker studies in Alzheimer's disease research: An updated review and consensus of the Salivary Biomarkers for Dementia Research Working Group.

There is a pressing need for accessible biomarkers with high diagnostic accuracy for Alzheimer's disease (AD) diagnosis to facilitate widespread screening, particularly in underserved groups. Saliva is an emerging specimen for measuring AD biomarkers, with distinct contexts of use that could complement blood and cerebrospinal fluid and detect various analytes. An interdisciplinary, international group of AD and related dementias (ADRD) researchers convened and performed a narrative review of published studies on salivary AD biomarkers.

Frequency, characteristics, and immunological accompaniments of ataxia in anti-NMDAR antibody-associated encephalitis.

Introduction: Very rarely, adult NMDAR antibody-associated encephalitis (NMDAR-E) leads to persistent cerebellar atrophy and ataxia. Transient cerebellar ataxia is common in pediatric NMDAR-E. Immune-mediated cerebellar ataxia may be associated with myelin oligodendrocyte glycoprotein (MOG), aquaporin-4 (AQP-4), kelch-like family member 11 (KLHL11), and glutamate kainate receptor subunit 2 (GluK2) antibodies, all of which may co-occur in NMDAR-E.

A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe.

Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal.

Neuroinflammatory pathways and potential therapeutic targets in neonatal post-hemorrhagic hydrocephalus.

Background: Post-hemorrhagic hydrocephalus (PHH) is a severe complication in premature infants following intraventricular hemorrhage (IVH). It is characterized by abnormal cerebrospinal fluid (CSF) accumulation, disrupted CSF dynamics, and elevated intracranial pressure (ICP), leading to significant neurological impairments.

Objective: This review provides an overview of recent molecular insights into the pathophysiology of PHH and evaluates emerging therapeutic approaches aimed at addressing its underlying mechanisms.

Diminished spinal cord perfusion despite distal aortic perfusion: an acute translational large animal experiment with occluded segmental arteries.

Objectives: Neuroprotective measures have been established in open thoraco-abdominal aortic aneurysm repair to reduce the incidence of postoperative paraplegia. Distal aortic perfusion (DaP) is meant to increase blood flow to the abdominal organs and the spinal cord. Cerebrospinal fluid (CSF) drainage is part of peri- and postoperative clinical routine.

Prognostic Relevance of Relative Ellipsoid Zone Reflectivity for Ellipsoid Zone Loss in Macular Telangiectasia Type 2.

Purpose: The relative ellipsoid zone reflectivity (rEZR) is an innovative biomarker for photoreceptor alterations and showed association with disease staging in macular telangiectasia type 2 (MacTel). However, its prognostic relevance for the ellipsoid zone (EZ) loss is unclear.

Methods: Longitudinal spectral-domain optical coherence tomography (SD-OCT) imaging of patients with MacTel from an observational natural history study was used for en face determination of manifest EZ loss.

BOLD-CSF dynamics assessed using real-time phase contrast CSF flow interleaved with cortical BOLD MRI.

Background: Cerebrospinal fluid (CSF) motion and pulsatility has been proposed to play a crucial role in clearing brain waste. Although its driving forces remain debated, increasing evidence suggests that large amplitude vasomotion drives such CSF fluctuations. Recently, a fast blood-oxygen-level-dependent (BOLD) fMRI sequence was used to measure the coupling between CSF fluctuations and low-frequency hemodynamic oscillations in the human cortex.

Long-term egg-protein hydrolysate consumption improves endothelial function: a randomized, double-blind, placebo-controlled trial in older adults with overweight or obesity.

Purpose: The dietary egg-protein hydrolysate Newtricious (NWT)-03 has previously demonstrated improvements in blood pressure and metabolic profiles. However, the long-term effects on vascular function and cardiometabolic risk markers are unknown.

Methods: Forty-four older (aged 60-75) adults with overweight/obesity experiencing elevated Subjective Cognitive Failures (SCF) were randomized into a 36-week, double-blind, placebo-controlled trial.

Herbal prescription Siryeongtang and acupuncture treatment for gait disturbance due to idiopathic normal pressure hydrocephalus: A case report.

Background: Idiopathic normal-pressure hydrocephalus (iNPH), characterized by unexplained normal-pressure hydrocephalus, primarily presents with symptoms such as gait disturbances, cognitive impairment, and urinary incontinence. Currently, cerebrospinal fluid (CSF) drainage via shunting is the only effective treatment for iNPH.

Case Presentation: A 56-year-old Asian woman visited our hospital with a worsening gait disturbance and a history of recurrent falls over the past 2 years.

Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is a rare immune-mediated polyradiculoneuropathy. Patients typically develop rapidly progressive weakness and sensory deficits that can result in complete paralysis requiring mechanical ventilation. GBS is usually a monophasic disease in which an aberrant immune response to an infection or other trigger damages the peripheral nerves.

Alzheimer's disease-associated CD83(+) microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagal nerve, and brain.

Introduction: While there may be microbial contributions to Alzheimer's disease (AD), findings have been inconclusive. We recently reported an AD-associated CD83(+) microglia subtype associated with increased immunoglobulin G4 (IgG4) in the transverse colon (TC).

Methods: We used immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments to explore this association.

Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7 immunorad conference.

Over the last decade, the annual Immunorad Conference, held under the joint auspicies of Gustave Roussy (Villejuif, France) and the Weill Cornell Medical College (New-York, USA) has aimed at exploring the latest advancements in the fields of tumor immunology and radiotherapy-immunotherapy combinations for the treatment of cancer. Gathering medical oncologists, radiation oncologists, physicians and researchers with esteemed expertise in these fields, the Immunorad Conference bridges the gap between preclinical outcomes and clinical opportunities. Thus, it paves a promising way toward optimizing radiotherapy-immunotherapy combinations and, from a broader perspective, improving therapeutic strategies for patients with cancer.

Implications of the choroid plexus in Niemann-Pick disease Type C neuropathogenesis.

Background: Niemann-Pick Disease Type C (NPC) is an ultra-rare disorder characterized by progressive psychiatric and neurologic manifestations, with late infantile, juvenile, and adolescent/adult presentations. We examined morphological properties of the choroid plexus, a protective blood-cerebrospinal fluid barrier, in NPC, and their relationship with neurodegeneration, clinical status, and circulatory markers. This study also determined whether choroid plexus morphology differentiates between NPC and more prevalent illnesses, schizophrenia (SZ) and bipolar disorder (BD), which have overlapping psychiatric symptoms with adolescent and adult-onset NPC and are associated with misdiagnosis.

Respiratory syncytial virus infection in patients with haematological diseases: a retrospective multicentre study.

Purpose: This study aims to evaluate the burden of respiratory syncytial virus (RSV) infections in patients with haematological diseases. It seeks to analyse the relevance of prevention, diagnosis and treatment of RSV infections.

Methods: A multi-centre, retrospective study was conducted across University Hospitals in Cologne, Düsseldorf, Bonn, and the University Medical Centre Hamburg-Eppendorf between Jan 2016 and Aug 2023.