Standardisierte Kontrastmittelsonographie (CEUS) in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin (CEUS-Akut)

Die Anaesthesiologie -     

The clinical dilemma of JAK inhibitor failure in myelofibrosis: Predictive characteristics and outcomes

Two Janus-associated kinase inhibitors (JAKi) (initially ruxolitinib and, more recently, fedratinib) have been approved as treatment options for patients who have intermediate-risk and high-risk myelofibrosis (MF), with pivotal trials demonstrating improvements in spleen volume, disease symptoms, and quality of life. At the same time, however, clinical trial experiences with JAKi agents in MF have demonstrated a high frequency of discontinuations because of adverse events or progressive disease. In addition, overall survival benefits and clinical and molecular predictors of response have not been established in this population, for which the disease burden is high and treatment options are limited. Consistently poor outcomes have been documented after JAKi discontinuation, with survival durations after ruxolitinib ranging from 11 to 16 months across several studies. To address such a high unmet therapeutic need, various non-JAKi agents are being actively explored (in combination with ruxolitinib in first-line or salvage settings and/or as monotherapy in JAKi-pretreated patients) in phase 3 clinical trials, including pelabresib (a bromodomain and extraterminal domain inhibitor), navitoclax (a B-cell lymphoma 2/B-cell lymphoma 2-xL inhibitor), parsaclisib (a phosphoinositide 3-kinase inhibitor), navtemadlin (formerly KRT-232; a murine double-minute chromosome 2 inhibitor), and imetelstat (a telomerase inhibitor). The breadth of data expected from these trials will provide insight into the ability of non-JAKi treatments to modify the natural history of MF.     

Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

The behaviour change techniques used by Australian physiotherapists to promote non-treatment physical activity to patients with musculoskeletal conditions

Objectives

To determine: (i) the behaviour change techniques used by a sample of Australian physiotherapists to promote non-treatment physical activity; and (ii) whether those behaviour change techniques are different to the techniques used to encourage adherence to rehabilitation exercises.

The Transmission of Trauma from Mother to Infant: Radioactive Residues and Counter-Transference in the Case of a Haitian Mother and Her Two-Year-Old Son*

ABSTRACT

Close observation of the interactions between a traumatised mother and her infant son provides information on the modes of transmission of psychic trauma in the mother–infant dyad. Following the presentation of a current literature review on the theme, the subject of “radioactive residue” and counter-transference in the transmission of psychic trauma from mother to infant will be illustrated through a clinical case study that focuses on a Haitian mother and her two-year-old infant son who has been referred to a “transitional care nursery” in urban Paris. The encounter with this mother–infant dyad is analysed through observing the quality of the interactions that take place between the mother and infant in order to determine how a particularly traumatic narrative impacts the mother–infant relationship, in addition to relations with the clinician. Mother and infant respond to one another through the emission and reception of “radioactive residues” as hypothesized by Gampel. This clinical case study shows that there is a need to consider transcultural factors and collective experience and history when analysing traumatic events. Additionally, the case study shows that counter-transference can be an effective clinical tool for gaining access to an infant's experience as the recipient of a traumatic narrative.