Citations

Abstract Aims Native T1 times from T1 mapping cardiac magnetic resonance (CMR) are associated with myocardial fibrosis in aortic stenosis (AS). We investigated whether changing patterns in native T1 predict clinical outcomes after aortic valve replacement (AVR) in severe AS patients. Methods and results Forty-three patients with severe AS (65.9 ± 8.1 years; 24 men) who underwent T1 mapping CMR at baseline and 1 year after AVR were prospectively enrolled. Upper limit of native T1 from healthy volunteers was used to define normal myocardium and diffuse fibrosis (native T1 < 1208.4 and ≥1208.4 ms, respectively). Participants were categorized into Group 1 (pre- and post-AVR normal myocardium; n = 11), Group 2 (pre-AVR diffuse fibrosis and post-AVR normal myocardium; n = 18), and Group 3 (post-AVR diffuse fibrosis; n = 14). Native T1 significantly decreased 1 year after AVR (pre-AVR, 1233.8 ± 49.7 ms; post-AVR, 1189.1 ± 58.4 ms; P < 0.001), which was associated with left ventricular (LV) mass regression (△native T1 vs. △LV mass index, r = 0.454, P = 0.010) and systolic function improvement (△native T1 vs. △LV ejection fraction, r = −0.379, P = 0.012). Group 2 showed greater functional improvements, whereas these benefits were blunted in Group 3. Group 3 had significantly worse outcomes than Group 1 [hazard ratio (HR), 9.479, 95% confidence interval (CI) 1.176–76.409; P = 0.035] and Group 2 (HR 3.551, 95% CI 1.178–10.704; P = 0.024). Conclusion AVR-induced changes in native T1 values are associated with LV systolic functional changes as well as prognosis in severe AS. Post-AVR T1 mapping CMR can be used as an imaging biomarker.

Key Points Cytokines in the BM microenvironment regulate PD-1 ligand expression and secretion in WM. Secreted PD-1 ligands modulate T-cell function in WM.

AbstractCellular studies indicate that endocannabinoid type‐1 retrograde signaling plays a major role in synaptic plasticity. Disruption of these processes by delta‐9‐tetrahydrocannabinol (THC) could produce alterations either in structural and functional brain connectivity or in their association in cannabis (CB) users. Graph theoretic structural and functional networks were generated with diffusion tensor imaging and resting‐state functional imaging in 37 current CB users and 31 healthy non‐users. The primary outcome measures were coupling between structural and functional connectivity, global network characteristics, association between the coupling and network properties, and measures of rich‐club organization. Structural–functional (SC–FC) coupling was globally preserved showing a positive association in current CB users. However, the users had disrupted associations between SC–FC coupling and network topological characteristics, most perturbed for shorter connections implying region‐specific disruption by CB use. Rich‐club analysis revealed impaired SC–FC coupling in the hippocampus and caudate of users. This study provides evidence of the abnormal SC–FC association in CB users. The effect was predominant in shorter connections of the brain network, suggesting that the impact of CB use or predispositional factors may be most apparent in local interconnections. Notably, the hippocampus and caudate specifically showed aberrant structural and functional coupling. These structures have high CB1 receptor density and may also be associated with changes in learning and habit formation that occur with chronic cannabis use.

Aims: Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease thought to be caused by repetitive traumatic brain injury (TBI) and subconcussive injuries. While hyperphosphorylation of tau (p-Tau), which is attributed to astrocytic tangles (ATs) and neurofibrillary tangles, is known to be involved in CTE, there are limited neuropathological or molecular data. By utilizing repetitive mild TBI (rmTBI) mouse models, our aim was to examine the pathological changes of CTE-associated structures, specifically the ATs. Results: Our rmTBI mouse models showed symptoms of depressive behavior and memory deficit, alongside an increased p-Tau expression in their neurons and astrocytes in both the hippocampus and cortex. rmTBI induced oxidative stress in endothelial cells and nitric oxide (NO) generation in astrocytes, which were mediated by hypoxia and increased hypoxia-inducible factor 1-α (HIF1α). There was also correlated decreased regional cerebral tissue perfusion units, mild activation of astrocytes and NFκB phosphorylation, increased expression of inducible nitric oxide synthase (iNOS), increased endothelial nitric oxide synthase (eNOS) uncoupling with decreased tetrahydrobiopterin, and increased expression of nitrotyrosine, NADPH oxidase 2 (Nox2)/nuclear factor (erythroid-derived 2) factor 2 (Nrf2) signaling proteins. Combined, these effects induced peroxynitrite formation and hyperphosphorylation of tau in the hippocampus and cortex toward the formation of ATs. Innovation: Our model features molecular pathogenesis events of CTE with clinically relevant latency periods. In particular, this is the first demonstration of an increased astrocytic iNOS expression in an in vivo model. Conclusion: We propose a novel mechanism of uncoupled eNOS and NO contribution to Tau phosphorylation and AT formation in rmTBI brain, toward an increased molecular understanding of the pathophysiology of human CTE.

Background: Debate exists about whether neuromyelitis optica spectrum disorder seronegative disease represents the same immune-mediated attack on astrocytic aquaporin-4 as in seropositive disease. Objective: We investigated whether response to common treatments for neuromyelitis optica spectrum disorder differed by serostatus, as assessed by change in annualized relapse rate. Methods: We performed a multicenter retrospective analysis of 245 patients with neuromyelitis optica spectrum disorder who were treated with either rituximab or mycophenolate mofetil as their first-line immunosuppressive treatment for disease prevention. Patients were followed for a minimum of 6 months following treatment initiation. Results: In those started on rituximab, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.81 and 1.93, respectively. On-treatment annualized relapse rates significantly declined to 0.32 (seropositive; p < 0.0001) and 0.12 (seronegative; p = 0.0001). In those started on mycophenolate mofetil, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.79 and 1.45, respectively. On-treatment annualized relapse rates declined to 0.29 (seropositive; p < 0.0001) and 0.30 (seronegative; p < 0.005). Conclusion: In this international collaboration involving a large number of neuromyelitis optica spectrum disorder patients, treatment was effective regardless of serostatus. This suggests that treatment should not differ when considering these treatments.