Immune system adaptation during gender-affirming testosterone treatment.

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 COVID1, similar to observations in other infections2. Females respond more strongly to vaccines, and adverse reactions are more frequent3, like most autoimmune diseases4. Immunological sex differences stem from genetic, hormonal and behavioural factors5 but their relative importance is only partially understood6-8. 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.

Normalized Interferon Signatures and Clinical Improvements by IFNAR1 Blocking Antibody (Anifrolumab) in Patients with Type I Interferonopathies.

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.

Manoeuvring between interplay and context- an ethnographic study of social interaction in encounters between registered nurses, older patients and their relatives.

BACKGROUND: Social interactions between registered nurses, older patients and their relatives are essential and play a central role in developing a successful care relationship in healthcare encounters. How nurses interact with patients affects the patient's well-being. Limited time and demands for efficiency influence the encounter and complaints from patients and relatives often concern social interactions. Therefore, the aim of this study was to explore the social interaction in encounters between registered nurses, older patients and their relatives at a department of medicine for older people. METHODS: The study has an ethnographic approach including participatory observations (n = 21) and informal field conversations (n = 63), followed by a thematic analysis with an abductive approach reflecting Goffman's interactional perspective. RESULT: The result revealed a pattern where the participants manoeuvred between interplay and context. By manoeuvring, they defined roles but also created a common social situation. Nurses led the conversation; patients followed and described their health problems, while relatives captured the moment to receive and provide information. Finally, nurses summarised the encounter using ritual language, patients expressed gratitude through verbal and non-verbal expressions, while relatives verbally confirmed the agreements. CONCLUSION: The social interaction between registered nurses, older patients and relatives was shaped by a pattern where the participants manoeuvred between interplay and context. When all participants assume responsibility for the social interaction, they become active and listen to each other. The approach adopted by nurses is crucial, thus training in communication and social interaction skills are important. When the asymmetry due to imbalance, is reduced, less misunderstanding and a satisfactory care relationship can be achieved.

Striving to establish a care relationship-Mission possible or impossible?-Triad encounters between patients, relatives and nurses.

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.

Voices used by nurses when communicating with patients and relatives in a department of medicine for older people-An ethnographic study.

AIMS AND OBJECTIVES: To describe how nurses communicate with older patients and their relatives in a department of medicine for older people in western Sweden. BACKGROUND: Communication is an essential tool for nurses when working with older patients and their relatives, but often patients and relatives experience shortcomings in the communication exchanges. They may not receive information or are not treated in a professional way. Good communication can facilitate the development of a positive meeting and improve the patient's health outcome. DESIGN: An ethnographic design informed by the sociocultural perspective was applied. METHODS: Forty participatory observations were conducted and analysed during the period October 2015-September 2016. The observations covered 135 hours of nurse-patient-relative interaction. Field notes were taken, and 40 informal field conversations with nurses and 40 with patients and relatives were carried out. Semistructured follow-up interviews were conducted with five nurses. RESULTS: In the result, it was found that nurses communicate with four different voices: a medical voice described as being incomplete, task-oriented and with a disease perspective; a nursing voice described as being confirmatory, process-oriented and with a holistic perspective; a pedagogical voice described as being contextualised, comprehension-oriented and with a learning perspective; and a power voice described as being distancing and excluding. The voices can be seen as context-dependent communication approaches. When nurses switch between the voices, this indicates a shift in the orientation or situation. CONCLUSION: The results indicate that if nurses successfully combine the voices, while limiting the use of the power voice, the communication exchanges can become a more positive experience for all parties involved and a good nurse-patient-relative communication exchange can be achieved. RELEVANCE TO CLINICAL PRACTICE: Working for improved communication between nurses, patients and relatives is crucial for establishing a positive nurse-patient-relative relationship, which is a basis for improving patient care and healthcare outcomes.

What are they talking about? Content of the communication exchanges between nurses, patients and relatives in a department of medicine for older people-An ethnographic study.

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.

Women's experiences of remote video calls with a labour ward midwife during early labour.

BACKGROUND: In an increasingly strained maternity care system with a shortage of midwives and great demands for service, pregnant women in their early labour are at risk of receiving insufficient support. Women make calls and visit the labour ward on multiple occasions before being admitted. A video call with a labour ward midwife during early labour is an unknown practice but could support pregnant women and their partners during this uncertain period. AIM: The study aimed to describe women's experiences of remote video calls with a labour ward midwife during early labour. METHODS: A qualitative study comprising nine semi-structured interviews followed by an inductive thematic analysis was conducted. RESULTS: The results revealed that video calls prepared women and their partners by means of practical support. They received an assessment of early labour and the interaction with labour ward midwives prepared them for the impending birth. The participants reported feeling secure and strengthened by being met at their current stage of labour. Furthermore, they found the service accessible, easy to use and emphasised the need for increased availability and continuity. CONCLUSION: This study highlights the positive impact of video calls in early labour when conducted by competent labour ward midwives. The perceived accessibility and ease of use e-health system underscore a demand for extended availability. These findings indicate the potential benefits of integrating video calls in labour care to enhance support, security, accessibility and overall satisfaction for pregnant women and their partners.

Autoantibodies to protein S may explain rare cases of coagulopathy following COVID-19 vaccination.

While Coronavirus disease 2019 (COVID-19) vaccines have proven to be both effective and generally safe, rare but severe adverse events following immunization (AEFIs) are described. Autoantibodies to platelet factor-4 are associated with catastrophic thrombotic AEFIs, but comprehensive investigations of other autoantibodies are lacking. We aimed to detect and describe autoantibodies targeting coagulation-related proteins in a population-wide cohort (SWEDEGENE) including AEFIs attributed to COVID-19 vaccines in Sweden. Subjects were recruited from December 2020 to October 2022 and were stratified based on diagnosis and COVID-19 exposure. Screening was carried out in two phases, with a multiplex bead-based assay in the first subset (until September 2021) and with targeted assays for the second (until October 2022). Positivity was defined based on absolute, relative, and biological/technical thresholds. Patients with coagulation-related AEFIs were older and the Vaxzevria vaccine was overrepresented in this group. Two cases had antiphospholipid antibodies but none had PF4 antibodies. We identified six positives for protein S autoantibodies. Protein S concentrations were negatively correlated with autoantibody response in patients with immunoreactivity and functional analysis revealed low protein S activity in three subjects. Our population-wide analysis reveals cases with autoantibodies against protein S which possibly underlie coagulopathic AEFIs.

Cytokine Profile in Children Following SARS-CoV-2 Infection: Preliminary Findings.

We provide preliminary evidence that, also in children, Long coronavirus disease (COVID) may be characterized by a proinflammatory signature. Ten Long COVID patients, 7 convalescent subjects after COVID infection and 4 healthy controls were enrolled. When adjusted for sex, children with long COVID had statistically significant differences in the levels of Flt3L, CD5, uPA, CCL23, CD40 and TGFα. When adjusted for age, CCL23 levels remained statistically significant.

No link between type I interferon autoantibody positivity and adverse reactions to COVID-19 vaccines.

Type I interferons act as gatekeepers against viral infection, and autoantibodies that neutralize these signaling molecules have been associated with COVID-19 severity and adverse reactions to the live-attenuated yellow fever vaccine. On this background, we sought to examine whether autoantibodies against type I interferons were associated with adverse events following COVID-19 vaccination. Our nationwide analysis suggests that type I interferon autoantibodies were not associated with adverse events after mRNA or viral-vector COVID-19 vaccines.