The role of CD8+ T-cell clones in immune thrombocytopenia.

Immune thrombocytopenia (ITP) is traditionally considered an antibody-mediated disease. However, a number of features suggest alternative mechanisms of platelet destruction. In this study, we use a multidimensional approach to explore the role of cytotoxic CD8+ T cells in ITP. We characterized patients with ITP and compared them with age-matched controls using immunophenotyping, next-generation sequencing of T-cell receptor (TCR) genes, single-cell RNA sequencing, and functional T-cell and platelet assays. We found that adults with chronic ITP have increased polyfunctional, terminally differentiated effector memory CD8+ T cells (CD45RA+CD62L-) expressing intracellular interferon gamma, tumor necrosis factor α, and granzyme B, defining them as TEMRA cells. These TEMRA cells expand when the platelet count falls and show no evidence of physiological exhaustion. Deep sequencing of the TCR showed expanded T-cell clones in patients with ITP. T-cell clones persisted over many years, were more prominent in patients with refractory disease, and expanded when the platelet count was low. Combined single-cell RNA and TCR sequencing of CD8+ T cells confirmed that the expanded clones are TEMRA cells. Using in vitro model systems, we show that CD8+ T cells from patients with ITP form aggregates with autologous platelets, release interferon gamma, and trigger platelet activation and apoptosis via the TCR-mediated release of cytotoxic granules. These findings of clonally expanded CD8+ T cells causing platelet activation and apoptosis provide an antibody-independent mechanism of platelet destruction, indicating that targeting specific T-cell clones could be a novel therapeutic approach for patients with refractory ITP.

Safety and efficacy of SARS-CoV-2 vaccination in patients with immune thrombocytopenia: A two-centre review.

Multiple studies have reported immune thrombocytopenia (ITP) relapse following SARS-CoV-2 vaccination, however baseline ITP relapse rate and antibody response to vaccination are not known. Patients with ITP who received at least one of the first three SARS-CoV-2 vaccination doses were included in the study. One hundred and twenty-four patients met the inclusion criteria. Relapse rate was 4.2% following a first vaccine dose, 9.1% after a second and 2.9% after a third; baseline relapse rate was 7.6%. Ninety-four per cent of patients who received three vaccine doses developed a clinical antibody response. SARS-CoV-2 vaccination appears to be safe and effective in patients with ITP.

Identification of occult cerebral microbleeds in adults with immune thrombocytopenia.

Management of symptoms and prevention of life-threatening hemorrhage in immune thrombocytopenia (ITP) must be balanced against adverse effects of therapies. Because current treatment guidelines based on platelet count are confounded by variable bleeding phenotypes, there is a need to identify new objective markers of disease severity for treatment stratification. In this cross-sectional prospective study of 49 patients with ITP and nadir platelet counts <30 × 109/L and 18 aged-matched healthy controls, we used susceptibility-weighted magnetic resonance imaging to detect cerebral microbleeds (CMBs) as a marker of occult hemorrhage. CMBs were detected using a semiautomated method and correlated with clinical metadata using multivariate regression analysis. No CMBs were detected in health controls. In contrast, lobar CMBs were identified in 43% (21 of 49) of patients with ITP; prevalence increased with decreasing nadir platelet count (0/4, ≥15 × 109/L; 2/9, 10-14 × 109/L; 4/11, 5-9 × 109/L; 15/25 <5 × 109/L) and was associated with longer disease duration (P = 7 × 10-6), lower nadir platelet count (P = .005), lower platelet count at time of neuroimaging (P = .029), and higher organ bleeding scores (P = .028). Mucosal and skin bleeding scores, number of previous treatments, age, and sex were not associated with CMBs. Occult cerebral microhemorrhage is common in patients with moderate to severe ITP. Strong associations with ITP duration may reflect CMB accrual over time or more refractory disease. Further longitudinal studies in children and adults will allow greater understanding of the natural history and clinical and prognostic significance of CMBs.

Staff and patient experiences of decision-making about continuous observation in psychiatric hospitals.

PURPOSE: Continuous observation of psychiatric inpatients aims to protect those who pose an acute risk of harm to self or others, but involves intrusive privacy restrictions. Initiating, conducting and ending continuous observation requires complex decision-making about keeping patients safe whilst protecting their privacy. There is little published guidance about how to balance privacy and safety concerns, and how staff and patients negotiate this in practice is unknown. To inform best practice, the present study, therefore, aimed to understand how staff and patients experience negotiating the balance between privacy and safety during decision-making about continuous observation. METHODS: Thematic analysis of qualitative interviews with thirty-one inpatient psychiatric staff and twenty-eight inpatients. RESULTS: Most patients struggled with the lack of privacy but valued feeling safe during continuous observation. Staff and patients linked good decision-making to using continuous observation for short periods and taking positive risks, understanding and collaborating with the patient, and working together as a supportive staff team. Poor decision-making was linked to insufficient consideration of observation's iatrogenic potential, insufficient collaboration with patients, and the stressful impact on staff of conducting observations and managing risk. CONCLUSIONS: Best practice in decision-making about continuous observation may be facilitated by making decisions in collaboration with patients, and by staff supporting each-other in positive risk-taking. To achieve truly patient-centred decision-making, decisions about observation should not be influenced by staff's own stress levels. To address the negative impact of staff stress on decision-making, it may be helpful to improve staff training, education and support structures.

Evaluation of an Integrated Fluency and Acceptance and Commitment Therapy Intervention for Adolescents and Adults Who Stutter.

PURPOSE: Developmental stuttering is a complex and multifaceted neurodevelopmental disorder that may cause pervasive negative consequences for adults who stutter (AWS). Historically, intervention for AWS has primarily addressed speech fluency, with less focus on the covert psychosocial aspects of the disorder. The purpose of this article is to report on a feasibility trial evaluating a novel integrated intervention that combines traditional stuttering management techniques with Acceptance and Commitment Therapy (ACT) for AWS. METHOD: Twenty-nine AWS participated in the feasibility trial. All participants successfully completed a combined fluency and ACT intervention, titled the fluency and Acceptance and Commitment Therapy for Stuttering (fACTS) Program. As this was a feasibility study, no control group was included. Intervention was administered by two certified practicing speech-language pathologists, over eight 60- to 90-min sessions. RESULTS: Generalized linear mixed modeling was used to determine change from pre- to post-intervention and follow-up. Significant pre- and post-intervention improvements in self-efficacy, psychosocial functioning, and psychological flexibility were observed, along with significant reductions in observable stuttering behaviors (i.e., stuttered speech frequency). Intervention gains for all variables of interest were maintained 3 and 6 months post-intervention. CONCLUSIONS: The fACTS Program was created to be a holistic and flexible intervention to promote self-efficacy beliefs and address stuttering-related psychosocial impacts and speech fluency goals of AWS. Preliminary results indicated positive improvement in all psychosocial outcomes (i.e., self-efficacy, psychosocial impact, and psychological flexibility) and observable speech fluency following completion of the program. Future clinical trials of the fACTS Program with an included control group will further investigate the mechanisms of change for the positive effects observed.

Illustrated State-of-the-Art Capsules of the ISTH 2024 Congress.

Here, we present a series of illustrated capsules from the State of the Art (SOA) speakers at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand. This year's Congress marks the first time that the International Society on Thrombosis and Haemostasis has held its flagship scientific meeting in Southeast Asia and is the first to be organized by an international Planning Committee. The Bangkok program will feature innovative science and clinical updates from around the world, reflecting the diversity and multidisciplinary growth of our field. In these illustrated SOA capsules, you will find an exploration of novel models of thrombosis and bleeding and biomaterial discoveries that can trigger or block coagulation. Thromboinflammation is now understood to drive many disease states, and the SOA speakers cover cellular and coagulation responses to COVID-19 and other infections. The theme of crosstalk between coagulation and inflammation expands with capsules on protein S signaling, complement, and fibrinolytic inhibitors. Novel agents for hemophilia and thrombosis prevention are introduced. Challenging clinical conditions are also covered, such as inherited platelet disorders and antiphospholipid antibody syndrome. The scientific program in Bangkok will also showcase the work of clinicians and scientists from all parts of the world and chronicle real-world challenges. For example, 2 SOA capsules address the diagnosis and management of von Willebrand disease in low-income settings. Take some time to browse through these short illustrated reviews; we're sure that you'll be entertained, educated, and inspired to further explore the world of thrombosis and hemostasis.

Evaluation of an integrated fluency and Acceptance and Commitment Therapy intervention for adolescents and adults who stutter: Participant perspectives.

PURPOSE: Childhood-onset stuttering is a neurodevelopmental disorder that may cause pervasive negative consequences for adults who stutter. In addition to significant challenges in personal, social, and emotional domains, stuttering has been shown to impose an economic burden on adults who stutter. Intervention for adults who stutter has historically addressed speech fluency more so than the covert psychosocial aspects of the disorder. There is an identified clinical need for holistic, efficacious, and cost-effective stuttering interventions that meet consumer needs. The purpose of the present study is to evaluate a novel, integrated intervention that combined traditional fluency techniques with Acceptance and Commitment Therapy, from the perspective of the adults who stutter who participated in the intervention. METHOD: Twenty-eight adults who stutter completed the intervention program. Participants were invited to complete an online post-program written survey (including qualitative comments) and a semi-structured interview to explore their evaluations of the program with respect to its authenticity, acceptability, and social validity. RESULTS: Participants perceived positive psychosocial changes as a result of the program, and were satisfied with the program overall. Qualitative thematic analyses of the written survey comments and the semi-structured interviews identified two major themes: factors specific to the intervention and factors specific to the therapeutic process. Several important sub-themes were also identified. CONCLUSION: Findings support the authenticity, acceptability, and social validity of an integrated fluency and psychosocial intervention for stuttering. Findings also highlight the need for consideration of the consumer voice in the management of stuttering disorders, in keeping with person-centred care.

Staff and patient perspectives on therapeutic engagement during one-to-one observation.

WHAT IS KNOWN ON THE SUBJECT?: One-to-one observation uses continuous staff observation to safeguard patients judged likely to harm themselves or others. Policies increasingly mandate that staff engage therapeutically with patients during one-to-one observation. Yet not enough is known about factors facilitating or impeding such therapeutic engagement. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: This study enriches existing literature on one-to-one observation through integrating the perspectives of staff of different levels of qualification, and patients of different diagnostic and risk profiles. Whilst previous research has highlighted the occurrence of counter-therapeutic staff-patient interactions, integration of patient and staff perspectives in the current study has demonstrated that patient and staff often attribute the causes differently, with each apportioning blame to the other, leading both parties to feel misunderstood, and staff lack confidence to overcome these challenges. A novel finding was that rapport-building via simple demonstrations of compassion and conversations about everyday things, was viewed as an essential prerequisite to encouraging patients to open up about their experiences of emotional distress, whilst implementation of techniques drawn from psychological interventions was viewed as less important than staff's core relational skills. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Therapeutic engagement during observation can enhance its risk management aims, providing thought is given to understanding and negotiating complex dynamics between staff and patients. Supervision for staff conducting observations should focus on building rapport in preference to emphasizing psychological intervention (e.g. DBT), and should enable staff to reflect on better understanding and managing their own emotions towards "hard-to-engage" patients. ABSTRACT: Introduction Policies increasingly focus on staff-patient interactions during one-to-one psychiatric nursing observations as an opportunity for therapeutic engagement - yet if and how this is feasible is unknown. Aim This study aimed to integrate staff and patient perspectives to determine what factors facilitate or impede therapeutic engagement during one-to-one observation. Method Thematic analysis of qualitative interviews with 31 psychiatric inpatient staff at different levels of seniority and 28 inpatients spanning a range of diagnoses and risk profiles. Results Negative experiences of observation were characterized by a reciprocal dynamic where both patients and staff withdrew from interactions, having felt the other did not want to engage with them. Staff and patients agreed that these difficulties could be overcome when staff showed patients that they cared, gradually building trust through simple demonstrations of compassion and 'normalizing' conversation about everyday things. This approach helped patients to feel safe enough to open up about their distress, which in turn helped staff to better understand their experiences and work with them to find solutions. Implications for practice Engagement during observation could be facilitated if staff receive more supervision in understanding difficult dynamics that impede rapport-building and in managing their emotions towards patients they experience as "hard-to-engage".