Case Report: Sudden very late-onset near fatal PD1 inhibitor-associated myocarditis with out-of-hospital cardiac arrest after >2.5 years of pembrolizumab treatment

IntroductionImmune checkpoint inhibitors have advanced the outcomes of many different types of cancer. A rare but extraordinarily severe complication of these agents resembles immune checkpoint inhibitor-related myocarditis, which typically occurs within the first few weeks after treatment initiation with a mortality of 25%–50%.Case reportA 57-year-old woman had uneventfully received pembrolizumab for metastatic non-small cell lung cancer for over 2.5 years and was admitted after an out-of-hospital cardiac arrest due to ventricular fibrillation. After successful cardiopulmonary resuscitation, the initial diagnostic work-up showed elevated cardiac enzymes and a limited left-ventricular ejection fraction, while coronary angiography did not show relevant stenosis. Despite cardiac MRI being unsuggestive of myocarditis, myocardial biopsies were obtained and histologically confirmed anti-PD-1 antibody-associated myocarditis. After the initiation of prednisone at 1 mg/kg body weight, the patient gradually recovered and was discharged three weeks later with markedly improved cardiac function.ConclusionThis case resembles the first description of a very late onset irMyocarditis, occurring over 2.5 years after the start of treatment. It demonstrates the importance of contemplating that severe immune-related toxicities with a sudden onset clinical presentation may occur even after long uneventful periods of anti-PD-1 immune checkpoint inhibitor treatment. Furthermore, it underlines the critical importance of myocardial biopsies in this setting, especially when cardiac MRI remains inconclusive. Moreover, it demonstrates the necessity and benefits of early immunosuppressive treatment if immune-related myocarditis is considered a differential diagnosis

Follow-up of the GHSG HD16 trial of PET-guided treatment in early-stage favorable Hodgkin lymphoma.

The primary analysis of the GHSG HD16 trial indicated a significant loss of tumor control with PET-guided omission of radiotherapy (RT) in patients with early-stage favorable Hodgkin lymphoma (HL). This analysis reports long-term outcomes. Overall, 1150 patients aged 18-75 years with newly diagnosed early-stage favorable HL were randomized between standard combined-modality treatment (CMT) (2x ABVD followed by PET/CT [PET-2] and 20 Gy involved-field RT) and PET-2-guided treatment omitting RT in case of PET-2 negativity (Deauville score [DS] < 3). The study aimed at excluding inferiority of PET-2-guided treatment and assessing the prognostic impact of PET-2 in patients receiving CMT. At a median follow-up of 64 months, PET-2-negative patients had a 5-year progression-free survival (PFS) of 94.2% after CMT (n = 328) and 86.7% after ABVD alone (n = 300; HR = 2.05 [1.20-3.51]; p = 0.0072). 5-year OS was 98.3% and 98.8%, respectively (p = 0.14); 4/12 documented deaths were caused by second primary malignancies and only one by HL. Among patients assigned to CMT, 5-year PFS was better in PET-2-negative (n = 353; 94.0%) than in PET-2-positive patients (n = 340; 90.3%; p = 0.012). The difference was more pronounced when using DS4 as cut-off (DS 1-3: n = 571; 94.0% vs. DS ≥ 4: n = 122; 83.6%; p < 0.0001). Taken together, CMT should be considered standard treatment for early-stage favorable HL irrespective of the PET-2-result

Perception of Loudness Is Influenced by Emotion

Loudness perception is thought to be a modular system that is unaffected by other brain systems. We tested the hypothesis that loudness perception can be influenced by negative affect using a conditioning paradigm, where some auditory stimuli were paired with aversive experiences while others were not. We found that the same auditory stimulus was reported as being louder, more negative and fear-inducing when it was conditioned with an aversive experience, compared to when it was used as a control stimulus. This result provides support for an important role of emotion in auditory perception

The Impact of Acute Psychosocial Stress on Magnetoencephalographic Correlates of Emotional Attention and Exogenous Visual Attention

Stress-induced acute activation of the cerebral catecholaminergic systems has often been found in rodents. However, little is known regarding the consequences of this activation on higher cognitive functions in humans. Theoretical inferences would suggest increased distractibility in the sense of increased exogenous attention and emotional attention. The present study investigated the influence of acute stress responses on magnetoencephalographic (MEG) correlates of visual attention. Healthy male subjects were presented emotional and neutral pictures in three subsequent MEG recording sessions after being exposed to a TSST-like social stressor, intended to trigger a HPA-response. The subjects anticipation of another follow-up stressor was designed to sustain the short-lived central catecholaminergic stress reactions throughout the ongoing MEG recordings. The heart rate indicates a stable level of anticipatory stress during this time span, subsequent cortisol concentrations and self-report measures of stress were increased. With regard to the MEG correlates of attentional functions, we found that the N1m amplitude remained constantly elevated during stressor anticipation. The magnetic early posterior negativity (EPNm) was present but, surprisingly, was not at all modulated during stressor anticipation. This suggests that a general increase of the influence of exogenous attention but no specific effect regarding emotional attention in this time interval. Regarding the time course of the effects, an influence of the HPA on these MEG correlates of attention seems less likely. An influence of cerebral catecholaminergic systems is plausible, but not definite

Übersicht der wichtigsten Regeln der englischen Syntax

vom Broeckelman

Landlose in Brasilien: Entstehungsbedingungen, Dynamik und Demokratisierungspotential der brasilianischen Landlosenbewegung

Bröckelmann-Simon M. Landlose in Brasilien: Entstehungsbedingungen, Dynamik und Demokratisierungspotential der brasilianischen Landlosenbewegung. Aspekte der Brasilienkunde ; 15. Mettingen: bkv, Brasilienkunde-Verl.; 1994