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Kardiovaskuläre Magnetresonanztomographie (Teil 1): Technik, Indikationen, Vorbereitung und Durchführung [Cardiovascular magnetic resonance imaging (Part 1): Technique, indications, preparation and performance]
No full textCardiovascular imaging is an essential component of modern cardiology. Its information is important for diagnosing cardiovascular diseases, for treatment decisions and therapy management, and for assessing individual prognosis. Magnetic resonance imaging (MRI) plays a growing role in this field. It provides information on cardiac anatomy, function, perfusion, viability, inflammation and blood flow. Frequent indications for cardiovascular MRI include the assessment of coronary artery disease, cardiomyopathies, inflammatory heart disease, heart failure, valvular heart disease and congenital heart defects. This two-part article provides a practical overview
Human T cells from resistant hypertension patients promote hypertension via TNF in humanized mice
Full text linkOBJECTIVE: Preclinical studies suggest a pivotal role of adaptive immunity, particularly T cells, in hypertension. However, due to the multifactorial pathogenesis, there is still no definitive evidence for a causal role of T cells in the development of hypertension in humans. We sought to determine whether T cells from patients with treatment-resistant hypertension (TRH) directly modulate blood pressure and vascular function in vivo. METHODS: Peripheral blood mononuclear cells (PBMCs) from TRH patients and healthy controls (HC) were adoptively transferred into immunodeficient NSG-(KbDb)^null mice. Hypertension was induced by angiotensin II infusion for 14 days and monitored continuously by radiotelemetry. RESULT: Following T cell engraftment, blood pressure was assessed at baseline and during AngII infusion in both groups of recipient mice. At baseline, systolic blood pressure did not differ between both groups. However, mice receiving TRH-PBMCs developed a significantly higher systolic blood pressure following AngII compared with HC-PBMC recipients. Endothelial dysfunction in isolated perfused kidneys was more pronounced in AngIIchallenged TRH-PBMC recipients compared to HC-PBMC recipients. TRH-PBMC recipients displayed elevated effector memory CD4(+) T cells and Th17 frequencies in spleen and kidney, along with markedly increased renal expression of human T cell-derived TNF. Overnight incubation of mouse aortic rings with human TNF induced endothelial dysfunction, indicating a causal role of T cell-derived TNF. As a proof of concept, TNF inhibition attenuated AngIIinduced hypertension in TRH-PBMC–engrafted mice. CONCLUSION: T cells from patients with treatment-resistant hypertension promote an exaggerated hypertensive response and endothelial dysfunction in PBMC-engrafted humanized mice, promoted by TNF-mediated mechanisms. These findings provide evidence that T cell–derived TNF may contribute to the pathogenesis of human hypertension
Cellular interactions and immunometabolic mechanisms in heart failure with preserved ejection fraction: from molecular mechanisms to clinical evidence
Full text linkHeart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome affecting ≈32 million individuals worldwide. It accounts for at least half of all heart failure cases and is associated with substantial morbidity and mortality. Although the prevalence of HFpEF increases with age, a substantial proportion of the HFpEF subjects present with cardiometabolic alterations, marking a specific phenogroup of HFpEF. Obesity, diabetes, and hypertension are considered central features in the pathophysiology of HFpEF, driving its development and disease progression by a complex interplay of metabolic-, hemodynamic-, and neurohormonal impairments, resulting in systemic inflammation and immune system dysregulation. Cellular and systemic immunometabolic stress induces vascular endothelial microvascular dysfunction, infiltration of immune cells in the myocardium, and activation of innate and adaptive immune cells in cardiac tissue. The resulting bidirectional crosstalk between systemic and cardiac metabolism influences immune cell reprogramming, sustaining a vicious cycle of cardiac chronic inflammatory response, ultimately leading to adverse structural and functional cardiac remodeling. In this review, we discuss the role of cellular interactions and immunometabolic mechanisms of immune system dysregulation resulting in cardiometabolic HFpEF and elaborate on therapeutic strategies targeting cardiometabolic risk
c-MAF transduces motor neuron firing to sustain fast-glycolytic myofibers and neuromuscular junctions
No full textThis study investigates how motoneuron firing influences transcription factor binding site enrichment in mouse fast glycolytic Myh4+ adult myofibers. Using single nucleus multi-omic analysis of innervated versus denervated tibialis anterior (TA) muscles, we identified a shift in transcription factor binding sites on active chromatin: SIX and c-MAF binding sites were enriched in Myh4+ myonuclei of innervated fibers but are replaced by JUN, FOS, and RUNX1 sites upon denervation. These findings suggest that c-MAF activity functions downstream of fast motoneuron firing. Supporting this, c-MAF shows robust nuclear enrichment in muscles stimulated at 100 Hz and during periods of increased motoneuron firing when mice are active, but is absent in denervated muscles. Thus, c-MAF bZIP transcription factor act as primary readouts of fast motoneuron firing in skeletal muscles. To clarify c-MAF’s regulatory network, constitutive and inducible skeletal muscle-specific c-Maf mutants were analyzed. Loss of cMAF resulted in atrophy of MYH4+ myofibers in specific distal hindlimb muscles, mirroring phenotypes seen in ALS and sciatic denervation models, while other muscles remained unaffected. Further, c-MAF was found to regulate neuromuscular junction (NMJ) stability. Following c-Maf deletion, NMJs became progressively fragmented, accompanied by increased motoneuron terminal sprouting and ectopic reinnervation of myofibers as demonstrated by kinetics following c-Maf deletion. Overall, this work establishes c-MAF as a critical mediator linking motoneuron firing to muscle gene regulation, fiber integrity, and NMJ maintenance in fast glycolytic fibers of specific muscles
MRD-2 in the GHSG HD21 trial assessed by a validated circulating tumor DNA sequencing assay
No full textBeyond cure, major goals in patients with Hodgkin lymphoma (HL) are tailoring treatment to a patient’s individual risk for relapse to reduce acute and late toxicities, identifying candidates for early incorporation of novel agents, and making treatment affordable on a global level. Minimal residual disease (MRD) assessment by circulating tumor (ct)DNA sequencing emerged as a promising strategy to achieve these goals; however, previous studies differed in sampling timepoints, assay validation, and definitions for MRD negativity. Here, we applied LymphoVista – a validated ctDNA sequencing assay for genotyping and MRD monitoring in lymphoma – to samples obtained from the GHSG HD21 trial following two cycles of treatment (MRD-2) using a case-cohort-design. Patients with positive MRD-2 were at higher risk for relapse, progression or death compared with MRD-2 negative patients (4-year progression-free survival (PFS): 36.7% vs. 82.2%; HR 5.3, 95%CI 2.0-13.8; p = 0.0008). Following inverse probability weighting accounting for the number of events in the full reference set, patients with positive and negative MRD-2 had 4-year PFS rates of 72.2% vs. 95.3%. By combining MRD-2 with PET-2, patients were stratified into three distinct groups regarding risk of relapse: low (MRD-2 negative and PET-2 negative), intermediate (MRD-2 positive or PET-2 positive), and high (MRD-2 positive and PET2 positive). In summary, these results suggest that assessment of MRD-2 by LymphoVista allows for early outcome prognostication in patients with HL and could be used as a tool to improve treatment guidance on its own or in conjunction with PET-2
Flexibility of cell fates and functions across sex determination systems revealed by comparative single-cell analyses
No full textSex determination in vertebrates can be initiated by a wide range of genetic or environmental triggers. Yet, the degree to which gonadal cell types and genetic programs are conserved remains unresolved. Here we employed single-cell transcriptomics to characterize the temperature-dependent sex determination (TSD) program in gonads from the turtle species Trachemys scripta. Comparative analyses against species with genetic sex determination, like mouse (XY) and chicken (ZW), revealed a marked divergence in cell type repertoires and functions during vertebrate evolution. Unlike mammals, fetal Leydig cells are absent from the early gonads of T. scripta , where the supporting lineage expresses genes required for androgen synthesis. Evolutionary reconstructions show that this lineage derives from a Pax2 -positive mesenchymal population, suggesting an ancestral condition in Archelosauria that differs from the primarily coelomic epithelium origin in the mammalian clade. Transcriptional dynamics and co-expression analyses revealed the recruitment of lineage-specific transcription factors, including Twist1 or Runx1 , into the genetic programs of vertebrate clades. Our findings reveal extensive plasticity of the cellular and genetic mechanisms of vertebrate sex determination and suggest that this flexibility is a key feature of gonadal evolution
Seeing elephants and drinking water from a porcelain vase - a case of septin-7 antibody-associated encephalitis presenting as a severe disorganized psychosis
Full text linkIdentifying autoimmune encephalitis (AIE) in patients with predominant psychiatric symptoms poses a diagnostic challenge for psychiatrists and neurologists, especially when CSF and MRI findings are inconclusive. We report a case of septin-7 AIE presenting as steroid-responsive psychosis, whose definite diagnosis could only be made years after onset
An update on the developments and challenges with the diagnosis and classification of autoimmune optic neuritis
No full textINTRODUCTION: Autoimmune optic neuritis (ON) is a heterogeneous spectrum that includes multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocytes glycoprotein antibody-associated disease (MOGAD), and rarer etiologies. Early and accurate attribution at the first attack is clinically decisive as treatment pathways diverge.
AREAS COVERED: This review synthesizes current knowledge on clinical signs and red flags as well as structured neuro-ophthalmic assessment with data on paraclinical tools including imaging, electrophysiology and fluid biomarkers. This issue is based on literature curated from PubMed/MEDLINE search (January 2000-June 2025; emphasis on 2022-2025) complemented by reference screening of key consensus criteria and landmark studies. Diagnostic gray zones are addressed, including seronegative and unclassified ON, along with practical implementation barriers such as protocol variability, assay access, optical coherence tomography (OCT) interoperability, and reimbursement. Artificial Intelligence (AI) applications for imaging data and mutli-parameter integration are outlined.
EXPERT OPINION: Real-world improvements will depend on standardized diagnostic pathways integrating orbital magnetic resonance imaging (MRI), high-quality antibody assays, OCT, and visual evoked potentials (VEP). Fluid biomarkers such as serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP), together with AI-supported analytics, may refine risk estimates, especially in seronegative cases
Dopaminergic sub-network connectivity alterations are associated with postoperative cognitive dysfunction: Results from the observational BioCog cohort study
No full textBACKGROUND: Postoperative cognitive dysfunction (POCD) is a detrimental complication after surgery with lasting impact on patients' daily lives. It is most common after postoperative delirium. While dopaminergic dysfunction has been suggested to play a role in delirium, little knowledge exists regarding its relevance for POCD.
OBJECTIVE: We hypothesised that POCD is associated with altered resting-state functional connectivity (FC) of the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNc) in functional magnetic resonance imaging (fMRI).
SETTING: Tertiary care centre, Germany.
PATIENTS: Patients aged at least 65 years with a Mini-Mental Status Examination (MMSE) at least 24 points presenting for elective major surgery were eligible for this study. Of 747 included patients, 214 patients with POCD assessment and at least one preoperative fMRI dataset were analysed.
INVESTIGATIONS: Resting-state fMRI and neuropsychological assessment before surgery and at follow-up 3 months later.
MAIN OUTCOME: POCD after 3 months after surgery was determined as the Reliable Change Index (RCI). Connectivity between VTA or SNc and 132 regions was calculated.
RESULTS: Twenty-six patients (12%) developed POCD. Four components for VTA-FC and SNc-FC were selected for further analysis with principal component analysis. For both VTA and SNc connectivity, one component was significantly associated with POCD. Postoperative alterations of dopaminergic networks were observed in an exploratory voxelwise analysis in a left temporal cluster.
CONCLUSION: Higher dopaminergic connectivity to regions associated with spatial perceptive processes and lower connectivity to cognitive control-related areas may predispose to POCD.
TRIAL REGISTRATION: clinicaltrials.gov, NCT02265263
Examining the contribution of childhood maltreatment to the gender gap in depression: insights from the German National Cohort (NAKO)
Full text linkBACKGROUND: Childhood maltreatment is a major risk factor for depression and may contribute to sex differences in depression prevalence. We examined sex-specific associations between childhood maltreatment and depression and estimated the proportion of depression cases attributable to specific maltreatment subtypes. METHODS: We analyzed baseline data from 159,045 participants (49.4% women; aged 19–72) in the German National Cohort (NAKO). Childhood maltreatment was assessed via the Childhood Trauma Screener; depression via self-reported physician’s diagnosis and MINI classification (lifetime) and the PHQ-9 (current). Associations, including sex interactions, were modeled using binary logistic regressions. Mediation analyses and sex-stratified population attributable fractions (PAFs) quantified the contribution of maltreatment to depression. RESULTS: Maltreatment was associated with increased odds of lifetime (OR(physician’s diagnosis)=2.45 [2.38,2.53]; OR(MINI)=2.30 [2.18,2.43]) and current depression (OR=2.90 [2.79,3.02]). Sex interactions were observed for the physician’s diagnosis: physical abuse and neglect had stronger associations in women (OR(physical abuse)=2.74 [2.59,2.90]; OR(physical neglect)=1.36 [1.28,1.44]) than men (OR(physical abuse)=2.36 [2.21,2.52]; OR(physical neglect)=1.08 [1.00,1.16]), whereas sexual abuse showed stronger associations in men (OR=3.23 [2.91,3.57]) than women (OR=2.61 [2.48,2.75]). Overall, childhood maltreatment accounted for 21.2-26.2% of lifetime and 33.4% of current depression. PAFs were higher in women than men for lifetime (24.5-28.5% vs. 16.0-20.9%) and current depression (36.1% vs. 28.2%). Emotional abuse and neglect contributed the highest PAFs (up to 10.2%). Maltreatment mediated 18.9-30.0% of the association between sex and depression. CONCLUSION: Maltreatment, especially emotional subtypes, account for a substantial proportion of depression in both sexes, with stronger overall associations in women. Sex-specific prevention may help reduce depression prevalence