Trametinib alters contractility of paediatric Noonan syndrome-associated hypertrophic myocardial tissue slices.

Aims: No curative treatment is available for RASopathy-associated childhood-onset hypertrophic cardiomyopathy (RAS-CM). Preclinical data and individual reports suggest a beneficial effect of small molecules targeting the RAS-mitogen-activated protein (MAP) kinase (MAPK) pathway in severely affected RAS-CM patients. The aim of this study was to evaluate the biophysical effects of trametinib, rapamycin and dasatinib on cultivated myocardial tissue slices of a paediatric RAS-CM patient using biomimetic cultivation chambers (BMCCs) and to correlate the findings with clinical data.

Overcoming age: Slow anesthesia induction may prevent geriatric patients from developing burst suppression and help developing intraoperative EEG signatures of a younger brain.

Elderly patients are prone to develop postoperative neurocognitive deficits potentially precipitated by inadequate anesthetic management. To investigate the potential of EEG-guided individualized anesthetic titration we evaluated the effect of the patient's age on the spectral composition of the EEG during slow propofol induction. Twenty-six young (<65 years) and 25 old (≥65 years) patients received propofol until loss of responsiveness (LOR).

An autoreactive T cell's perception of a land of plenty.

Understanding the nature of human autoantigen-specific CD4 T cells is limited by the difficulty of characterizing these cells ex vivo. In this issue of Immunity, Saggau et al. use ARTE technology to profile CD4 T cells specific to disease-relevant autoantigens and find that such cells develop an exhausted phenotype that includes FOXP3 expression and persist for extended periods of time.

Comprehensive sequential genetic analysis delineating frequency, patterns, and prognostic impact of genomic dynamics in a real-world cohort of patients with lower-risk MDS.

The acquisition of subsequent genetic lesions (clonal evolution, CE) and/or the expansion of existing clones (CEXP) contributes to clonal dynamics (CD) in myelodysplastic syndromes (MDS). Although CD plays an important role in high-risk patients in disease progression and transformation into acute myeloid leukemia (AML), knowledge about CD in lower-risk MDS (LR-MDS) patients is limited due to lack of robust longitudinal data considering the long clinically stable courses of the disease. In this retrospective analysis, we delineate the frequency and the prognostic impact of CD in an unselected real-world cohort of LR-MDS patients.

Impact of Age on the Occurrence of Processed Electroencephalographic Burst Suppression.

Background: Patient age is assumed to be an important risk factor for the occurrence of burst suppression, yet this has still to be confirmed by large datasets.

Methods: In this single-center retrospective analysis at a university hospital, the electronic patient records of 38,628 patients (≥18 years) receiving general anesthesia between January 2016 and December 2018 were analyzed. Risk factors for burst suppression were evaluated using univariate and multivariable analysis.

Effect of transcranial direct current stimulation and narrow-band auditory stimulation on the intraoperative electroencephalogram: an exploratoratory feasibility study.

Introduction: During general anesthesia, frontal electroencephalogram (EEG) activity in the alpha frequency band (8-12 Hz) correlates with the adequacy of analgesia. Transcranial direct current stimulation (tDCS) and auditory stimulation, two noninvasive neuromodulation techniques, can entrain alpha activity in awake or sleeping patients. This study evaluates their effects on alpha oscillations in patients under general anesthesia.

Preventing long-term disability in CIDP: the role of timely diagnosis and treatment monitoring in a multicenter CIDP cohort.

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an inflammatory disease affecting the peripheral nerves and the most frequent autoimmune polyneuropathy. Given the lack of established biomarkers or risk factors for the development of CIDP and patients' treatment response, this research effort seeks to identify potential clinical factors that may influence disease progression and overall treatment efficacy.

Methods: In this multicenter, retrospective analysis, we have screened 197 CIDP patients who presented to the University Hospitals in Düsseldorf, Berlin, Cologne, Essen, Magdeburg and Munich between 2018 and 2022.

B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4.

Neuromyelitis optica is a paradigmatic autoimmune disease of the central nervous system, in which the water-channel protein AQP4 is the target antigen. The immunopathology in neuromyelitis optica is largely driven by autoantibodies to AQP4. However, the T cell response that is required for the generation of these anti-AQP4 antibodies is not well understood.