Anette Johnsson

Abstract Infectious, inflammatory and autoimmune conditions present differently in males and females. SARS-CoV-2 infection in naive males is associated with increased risk of death, whereas females are at increased risk of long COVID 1 , similar to observations in other infections 2 . Females respond more strongly to vaccines, and adverse reactions are more frequent 3 , like most autoimmune diseases 4 . Immunological sex differences stem from genetic, hormonal and behavioural factors 5 but their relative importance is only partially understood 6–8 . In individuals assigned female sex at birth and undergoing gender-affirming testosterone therapy (trans men), hormone concentrations change markedly but the immunological consequences are poorly understood. Here we performed longitudinal systems-level analyses in 23 trans men and found that testosterone modulates a cross-regulated axis between type-I interferon and tumour necrosis factor. This is mediated by functional attenuation of type-I interferon responses in both plasmacytoid dendritic cells and monocytes. Conversely, testosterone potentiates monocyte responses leading to increased tumour necrosis factor, interleukin-6 and interleukin-15 production and downstream activation of nuclear factor kappa B-regulated genes and potentiation of interferon-γ responses, primarily in natural killer cells. These findings in trans men are corroborated by sex-divergent responses in public datasets and illustrate the dynamic regulation of human immunity by sex hormones, with implications for the health of individuals undergoing hormone therapy and our understanding of sex-divergent immune responses in cisgender individuals.

AIMS AND OBJECTIVES: To explore and describe the content of the communication exchanges between nurses, patients and their relatives in a department of medicine for older people in western Sweden. BACKGROUND: Information, messages and knowledge are constantly being communicated between nurses, older patients and relatives in the healthcare sector. The quality of communication between them has a major influence on patient outcomes. A prerequisite for good care to be given and received is that there is mutual understanding between the parties involved. DESIGN: An ethnographic study was informed by a sociocultural perspective. METHOD: Data were collected through 40 participatory observations of meetings between nurses and older patients and/or relatives which covered 135 hr of nurse-patient-relative interaction, field notes, 40 field conversations with 24 nurses and 40 field conversations with patients (n = 40) and relatives (n = 26). Five semi-structured interviews were conducted with nurses. An ethnographic analysis was performed. RESULTS: The analysis identified three categories of content of the communication exchanges: medical content focusing on the patient's medical condition, personal content focusing on the patient's life story and explanatory content focusing on the patient's health and nursing needs. The content is influenced by the situation and context. CONCLUSIONS: Nurses would benefit from more awareness and understanding of the importance of the communication content and of the value of asking the didactic questions (how, when, what and why) to improve the patients' and relatives' understanding of the information exchanges and to increase patient safety. RELEVANCE TO CLINICAL PRACTICE: Nurses can use the communication content to create conditions enabling them to obtain a holistic view of the patient's life history and to develop an appropriate person-centred care plan.

PURPOSE: A causal role of type-I interferons (IFN-I) in autoinflammatory type-I interferonopathies such as SAVI (STING-associated vasculopathy with onset in infancy) and CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures) is suggested by elevated expression of IFN-I stimulated genes (ISGs). Hitherto, the lack of specific inhibitors of IFN-I signaling has prevented the verification of a causal role for IFN-I in these conditions. Commonly used inhibitors of the JAK/STAT pathway exert broad effects on multiple signaling pathways leading to more general immunosuppression beyond IFN-I signaling. METHODS: Here we show in four patients with SAVI and one patient with CANDLE syndrome that blockade of the IFNAR1 receptor (Anifrolumab) exerts an additive effect over JAK-inhibitor alone. In two patients with SAVI, monotherapy with Anifrolumab is sufficient to retain a suppressed IFN-I signature and clinical improvement. RESULTS: Anifrolumab normalizes IFN-I signature genes and relieves symptoms beyond what is typically achieved by a JAK-inhibitor (Baricitinib) alone in patients with type-I interferonopathies. In two patients Anifrolumab was used successfully as monotherapy. Addition of Anifrolumab enabled steroid tapering and cessation with reduced overall immunosuppression and lower risks of opportunistic infections and improved metabolic states and growth which is highly beneficial in these young patients. CONCLUSION: These results verify a causal role of IFN-I signaling in type-I Interferonopathies SAVI and CANDLE and suggests Anifrolumab as an important new treatment option in autoinflammatory diseases with elevated IFN-I induced gene expression. Genia Kretzschmar, Laura Piñero Páez, and Ziyang Tan are shared-first authors. Sara Alehashemi, AnnaCarin Horne, and Petter Brodin are co-senior author.

The human blood proteome provides a holistic readout of health states through the assessment of thousands of circulating proteins. In this study, we present a pan-disease resource to enable the study of diverse disease phenotypes within a harmonized proteomics dataset. By profiling protein concentrations across 59 diseases and healthy cohorts, we identified proteins associated with age, sex, and body mass index, as well as disease-specific signatures. This study highlights shared and distinct protein patterns across conditions, demonstrating the power of a unified proteomics approach to uncover biological insights. The dataset, covering 8262 individuals and up to 5416 proteins, serves as an online resource for exploring disease-specific protein profiles and advancing precision medicine research.

BACKGROUND: When patients, relatives and nurses meet, they form a triad that can ensure a good care relationship. However, hospital environments are often stressful and limited time can negatively affect the care relationship, thus decreasing patient satisfaction. OBJECTIVE: To explain the care relationship in triad encounters between patients, relatives and nurses at a department of medicine for older people. DESIGN: A qualitative explorative study with an ethnographic approach guided by a sociocultural perspective. METHOD: Participatory observations and informal field conversations with patients, relatives and nurses were carried out from October 2015-September 2016 and analysed together with field notes using ethnographic analysis. RESULT: The result identifies a process where patients, relatives and nurses use different strategies for navigating before, during and after a triad encounter. The process is based on the following categories: orienting in time and space, contributing to a care relationship and forming a new point of view. CONCLUSION: The result indicates that nurses, who are aware of the process and understand how to navigate between the different perspectives in triad encounters, can acknowledge both the patient's and relatives' stories, thus facilitating their ability to understand the information provided, ensure a quality care relationship and strengthen the patient's position in the health-care setting, therefore making the mission to establish a care relationship possible.