Comprehensive morphologic characterization of bone marrow biopsy findings in a large cohort of patients with VEXAS syndrome: A single-institution longitudinal study of 111 bone marrow samples from 52 patients.

OBJECTIVES: VEXAS syndrome is an adult-onset autoinflammatory disease caused by a somatic pathogenic mutation in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. Patients present with rheumatologic manifestations and cytopenias and may have an increased predisposition to myelodysplastic syndrome (MDS) and plasma cell neoplasms. Prior studies have reported on the peripheral blood and bone marrow findings in patients with VEXAS syndrome. Due to the protean clinical presentation and lack of specificity of morphologic features (eg, vacuoles in early erythroid and granulocytic precursors), an optimal screening methodology to identify these patients in a timely fashion is desirable. METHODS: To further evaluate and describe the salient diagnostic morphologic features in VEXAS syndrome, we carried out a comprehensive study of the largest single-institution cohort to date. Diagnostic and follow-up bone marrow biopsy specimens from 52 male patients with molecularly identified VEXAS syndrome underwent central review. RESULTS: Cytopenias were common in all cases, primarily macrocytic anemia, monocytopenia, and thrombocytopenia. Bone marrow aspirate and biopsy were often hypercellular, with an increased myeloid/erythroid ratio, granulocytic hyperplasia with left shift, erythroid left shift, and megakaryocyte hyperplasia, which exhibited a range of striking morphologic findings. Distinctly vacuolated myeloid and erythroid precursors were seen in more than 95% of cases. CONCLUSIONS: Our data reveal potential novel diagnostic features, such as a high incidence of monocytopenia and distinct patterns of atypical megakaryopoiesis, that appear different from dysmegakaryopoiesis typically associated with MDS. In our experience, those findings are suggestive of VEXAS, in the appropriate clinical context.

Aggressive B-cell non-Hodgkin lymphomas: a report of the lymphoma workshop of the 20th meeting of the European Association for Haematopathology.

Aggressive B-cell non-Hodgkin lymphomas are a heterogeneous group of diseases and our concepts are evolving as we learn more about their clinical, pathologic, molecular genetic features. Session IV of the 2020 EAHP Workshop covered aggressive, predominantly high-grade B-cell lymphomas, many that were difficult to classify. In this manuscript, we summarize the features of the submitted cases and highlight differential diagnostic difficulties. We specifically review issues related to high-grade B-cell lymphomas (HGBCLs) with MYC and BCL2 and/or BCL6 rearrangements including TdT expression in these cases, HGBCL, not otherwise specified, large B-cell lymphomas with IRF4 rearrangement, high-grade/large B-cell lymphomas with 11q aberration, Burkitt lymphoma, and pleomorphic mantle cell lymphoma. Since the workshop, the 5th edition of the WHO Classification for Haematolymphoid Tumours (WHO-HAEM5) and International Consensus Classification (ICC) 2022 were published. We endeavor to use the updated terminology.

Goal setting as part of a holistic intervention to promote independence in older people with mild frailty: a process evaluation alongside a randomised controlled trial.

BACKGROUND: Frailty is a condition resulting from a decline in physiological reserves caused by an accumulation of several deficits, which progressively impairs the ability to recover from health adverse events. Following a promising feasibility study, the HomeHealth trial assessed a holistic tailored intervention for older adults with mild frailty to promote independence in their own homes, compared with usual care. We aimed to understand how goal setting worked among older people with mild frailty. METHODS: This study was a process evaluation alongside the HomeHealth randomised trial in older adults with mild frailty. The intervention was delivered at participants' homes, either in person or by telephone or videoconferencing. We carried out semi-structured interviews with older participants who had received the intervention (between three and six appointments), on average 233 days (range 68-465) after their last appointment, purposively sampled according to age, gender, number of sessions attended, adverse events, ethnicity, Index of Multiple Deprivation, Montreal Cognitive Assessment (MoCA) and Barthel scores, research site, and HomeHealth worker. We also conducted interviews with HomeHealth workers who delivered the intervention (n=7). Interviews explored the experience and process of goal setting, benefits and challenges, perceived progress, and behaviour change maintenance after the service had finished. Ethics approval was obtained, and all participants gave informed consent. Interviews were thematically analysed. HomeHealth workers kept formal records of goals set and assessed progress towards goals (0-2 rating scale) during six monthly-sessions, which were descriptively summarised. FINDINGS: 56 interviews were completed between July 15, 2022, and May 18, 2023. Study participants (n=49) had a mean age of 80 years (range 66-94), including 32 (65%) women and 17 (35%) men. Participants self-identified as White (n=42), Asian (n=3), Black (n=2), Mixed (n=1), and other ethnic (n=1) backgrounds. Findings suggested goal setting could be both a challenge and a motivator for older participants with mild frailty. Goal setting worked well when the older person could identify a clear need and set realistic goals linked to functioning, which led to a positive sense of achievement. Challenges occurred when older people were already accessing multiple resources and health services, or where the terminology of "goals" was off-putting due to work or school connotations. Average progress towards goals was 1·15/2. Most participants set goals around improving mobility (or a combination of mobility and another goal type such as socialising), and there was evidence of participants sustaining these behaviour changes after the intervention. INTERPRETATION: Older people with mild frailty can engage well with goal setting to promote independence. The lapse between receiving the intervention and being interviewed limited recall for some participants. However, the acceptability and adherence to the intervention for older people with mild frailty, and their moderate progress towards goals, should encourage further tailored and person-centred practices to promote their independence. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment.

The spectrum of nodular lymphocyte predominant Hodgkin lymphoma: a report of the lymphoma workshop of the 20th meeting of the European Association for Haematopathology.

Session 4 of the 2021 European Association of Haematopathology/Society for Hematopathology Workshop focused on nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). First, the spectrum of immunophenotypic variations in NLPHL and the defining criteria for classic Hodgkin Lymphoma (CHL) were discussed. The added value of further immunophenotypic characterization of both tumor cells and microenvironment to support the differential diagnosis was presented. Next, unusual cases with combined growth patterns and evolution of morphological features over time were presented to explore the clinicopathological impact of presumed high-risk patterns. Based on a large collection of cases, the defining morphological, immunophenotypical, and gene expression features of T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) and THRLBCL-like NLPHL (pattern E) were reviewed to explore this challenging differential diagnosis and critically evaluate whether aggressive behavior and transformation of NLPHL can be predicted in practice.

Mediastinal large B cell lymphoma and surrounding gray areas: a report of the lymphoma workshop of the 20th meeting of the European Association for Haematopathology.

Session 3 of the 2021 European Association for Haematopathology/Society for Hematopathology Workshop focused on mediastinal large B cell lymphomas and surrounding gray areas. One half of the session was dedicated to primary mediastinal large B cell lymphoma (PMBL) and included cases with classic clinicopathologic features, as well as cases with either morphologic or immunophenotypic variation, and PMBL-like cases with primary extramediastinal disease. The role of additional immunophenotyping and/or molecular testing to aid in the diagnosis of PMBL was discussed. The second half of the session focused on mediastinal and non-mediastinal gray zone lymphomas (GZL) with features intermediate between diffuse large B cell lymphoma (DLBCL) and classic Hodgkin lymphoma (CHL). Several cases illustrating the current challenges in separating this entity from PMBL/DLBCL and CHL were presented. There was discussion regarding the clinical and genetic differences between mediastinal and non-mediastinal GZLs. Rare cases of PMBL and GZL associated with EBV or follicular lymphoma were reviewed. Finally, several cases included in the session highlighted composite or sequential CHL and PMBL/DLBCL and/or GZL, highlighting challenges in separating such cases from GZL.

Lymphomas with plasmablastic features: a report of the lymphoma workshop of the 20th meeting of the European Association for Haematopathology.

Lymphomas with plasmablastic features are a heterogeneous group of aggressive and mostly uncommon neoplasms of varied aetiologies, presenting in immunocompetent individuals as well as in immunodeficiency, associated with EBV and Kaposi sarcoma virus infections, and some as progression from indolent B-cell lymphomas. They show overlapping diagnostic features and pose a differential diagnosis with other aggressive B-cell lymphomas that can downregulate the B-cell expression programme. The spectrum of rare reactive proliferations and all lymphomas defined by plasmablastic features, together with an expanding range of poorly characterised, uncommon conditions at the interface between reactive lymphoid proliferations and neoplasia submitted to the session V of the 20th European Association for Haematopathology/Society for Hematopathology lymphoma workshop are summarised and discussed in this paper.

Knowledge, Attitudes and Practices of Pregnant Women and Healthcare Providers in Bangladesh regarding Multivitamin Supplements during Pregnancy.

Micronutrient deficiencies are widespread among pregnant women in low- and middle-income countries (LMIC) and lead to potentially adverse effects for mother and baby. In Bangladesh, maternal malnutrition remains a severe problem, with high rates of anemia (49.6% of pregnant women and 47.8% of lactating women are anemic) and other nutritional deficiencies. A Knowledge, Attitudes, and Practices (KAP) study was conducted to assess Bangladeshi pregnant women's perceptions and related behaviors, as well as awareness and knowledge among pharmacists and healthcare professionals concerning prenatal multivitamin supplements. This was done in both rural and urban areas across Bangladesh. A total of 732 quantitative interviews were conducted (330 with providers and 402 with pregnant women, with an equal split between urban and rural areas for both sets of audiences; 200 women were users of prenatal multivitamin supplements, while 202 women were aware non-users). The study identified a few findings that can guide further research or market-based interventions to reduce micronutrient deficiencies. These include most pregnant women not knowing the right time to start multivitamin supplements (56.0%, [n = 225], stating that a woman should start taking supplements 'after the first trimester'), not knowing their benefits, and how they help both the mother and baby-only 29.5% [n = 59] stated that they believed the supplements helped their baby to grow well). Further, barriers to taking the supplements include women believing a nutritious diet is a substitute (88.7% [n = 293]), and a perceived lack of support from other family members (21.8%, [n = 72]). This suggests that there is a need for further awareness-raising among all pregnant women, their family members, and providers.

Predictors of engagement with peer support: analysis of data from a randomised controlled trial of one-to-one peer support for discharge from inpatient psychiatric care.

BACKGROUND: A range of evidence for the effectiveness of one-to-one peer support in mental health services is emerging. Levels of engagement with peer support vary with limited studies showing few individual participant characteristics predicting engagement. Implementation factors that might predict engagement have not been considered. METHODS: Data were analysed from the intervention arm of the ENRICH trial of one-to-one peer support for discharge from acute psychiatric inpatient care. Two outcomes were considered: (1) a measure of 'engaged with peer worker'; (2) number of face-to-face contacts with peer worker post-discharge. Two sets of independent variables were analysed against each outcome: (1) pre-randomisation participant characteristics; (2) implementation factors measured pre-discharge. Analyses used logistic and zero-inflated negative binomial regression models according to outcome structure. RESULTS: Data were analysed for 265 participants randomised to peer support who had a known peer worker. Non-heterosexual participants had increased odds of engaging with peer support compared to heterosexual participants, OR = 4.38 (95% CI: 1.13, 16.9, p = .032). Longer duration of first contact with peer worker (OR = 1.03, 95% CI: 1.00, 1.04, p < .001) and more relationship building activities in the first contact (OR = 1.4, 95% CI: 1.13, 1.85, p = .004) were associated with greater odds of engaging with peer support. Analysis of number of contacts post-discharge showed consistent findings. CONCLUSIONS: Implementation of peer support should include a focus on relationship building in the first session of peer support. The potential for peer support to break down barriers to accessing mental health services experienced by people from marginalised communities warrants further investigation.

What are the Challenges and Resilience Resources Identified by Informal Carers During the First UK COVID-19 Lockdown? A Longitudinal Qualitative Study Using Naturalistic Data.

COVID-19 has posed serious challenges for informal carers living in the UK. This article examines some of the specific challenges facing carers and the resources they used to manage them throughout the first UK lockdown. We used a framework approach to analyse naturalistic, longitudinal data from 30 carers taking part in 96 of Mobilise's daily Virtual Cuppas between March and July 2020. We found that lack of information and social restrictions cumulatively impacted carers' sense of certainty, control and motivation. This took an emotional toll on the carers, leading to exhaustion and burden. However, carers quickly established new routines and used humour and self-care to actively manage their wellbeing. Carers received support but also provided it to those in need, including fellow members of the caregiving community, supporting an ecological approach to carer resilience. Our findings may be used to anticipate challenges and promote protective resilience resources in future lockdowns.

Characterizing inflammatory profiles of suicidal behavior in adolescents: Rationale and design.

BACKGROUND: The suicide rate in youth and young adults continues to climb - we do not understand why this increase is occurring, nor do we have adequate tools to predict or prevent it. Increased efforts to treat underlying depression and other disorders that are highly associated with suicide have had limited impact, despite considerable financial investments in developing and disseminating available methods. Thus, there is a tremendous need to identify potential markers of suicide behavior for youth during this high-risk period. METHODS: Funded by the American Foundation for Suicide Prevention (AFSP), this study aims to map immune dysfunction to suicidal behavior and establish a reliable immune signature of suicide risk that can 1) guide future research into fundamental pathophysiology and 2) identify targets for drug development. The study design is an observational study where blood samples and a comprehensive array of clinical measures are collected from three groups of adolescents (n = 75 each) (1) with suicidal behavior [recent (within 3 months) suicide attempt or suicidal ideation warranting urgent evaluation,] (2) at risk for mood disorders, and (3) who are healthy (no psychiatric history). Participants will complete self-report and clinical assessments, along with a blood draw, at baseline, 3 months, 6 months and 12 months, and online self-report assessments once a month. RESULTS: The recruitment for this study is ongoing. LIMITATIONS: Observational, variability in treatment regimens. CONCLUSIONS: This study will help elucidate immune mechanisms that may play a causal role in suicide and serve as targets for future therapeutic development.

Transformation of FL into DLBCL with a PMBL gene expression signature.

We investigated the clinicopathologic features of 5 follicular lymphomas (FLs) that transformed (tFL) morphologically to diffuse large B-cell lymphomas (DLBCLs) and had a primary mediastinal large B-cell lymphoma (PMBL)-like gene expression profile (tFL-PMBLsig-pos). None of the tFL-PMBLsig-pos cases arose in the mediastinum, all cases tested had a germinal center B-cell phenotype, 20% were CD30+, 60% CD23+, 80% MAL+, 20% CD200+, and 0% CD273/PDL2+. Whole-exome sequencing detected alterations in genes associated with both FL/DLBCL (CREBBP, KMT2C, KMT2D, ARID1A, HIST1 members, and TNFRSF14) and PMBL (JAK-STAT pathway genes, B2M, and CD58). Copy number (CN) analysis detected gains/amplification of REL and STAT6 in 60%, gains of SOCS1 in 40%, and gains of chromosome 16, including IL4R, in 40% of the cases. CN gains/amplification of BCL6 and MYC and loss of TNFRSF14 and TNFAIP3 were identified in 20% of the cases. Three of 5 cases lacked a BCL2 rearrangement. Despite having some features that are less common in DLBCL (MAL and CD23 expression and JAK-STAT activation), these tFL-PMBLsig-pos cases lack the most characteristic CN alteration seen in PMBL (9p24.1 gain/amplification). This cohort expands the biologic heterogeneity of tFL, illustrating a subset with gene expression and some genetic features reminiscent of PMBL, with potential treatment implications that include the use of novel targeted therapies.

Respect for the journey: a survivor-led investigation of undergoing psychotherapy assessment.

PURPOSE: Psychotherapy assessments are key decision points for both clients and services, carrying considerable weight on both sides. Limited research indicates that assessments have immediate and long-term impacts on clients, particularly where trauma has been experienced, affecting engagement with therapy. Understanding assessments from clients' perspectives can inform service development and improve client experience. METHODS: This is a survivor-led exploration of clients' experiences of undergoing assessment for talking therapies. Interviews were conducted with seven people who had undergone assessment for psychological therapies in third sector and NHS services. Interviews were recorded, transcribed and analysed thematically. RESULTS: The core theme was 'respect for the journey' reflecting the need expressed by participants for their life experiences prior to the assessment to be given full respect and consideration. Six sub-themes were identified: trauma and desperation, fear of judgement, search for trust and safety, sharing and withholding (a balancing act), feeling deconstructed, and finding hope. CONCLUSIONS: The findings highlight the heightened emotional power surrounding psychotherapy assessments, reflecting the journey participants had undertaken to reach this point. The dilemma facing clients at the heart of an assessment-how much to share and how much to withhold-demonstrates the importance for services and assessors of treating the journey a client has made to the assessment with care and respect. Findings indicate the value of services and practitioners undertaking a trauma-informed approach to assessment encounters.

A comprehensive intervention package improves the linear growth of children under 2-years-old in rural Bangladesh: a community-based cluster randomized controlled trial.

Approximately one-third of children under the age of five are stunted in developing countries and many of them are micronutrient-deficient. We designed a comprehensive intervention package including egg/milk-based snacks to improve linear growth and dietary diversity among 6 to 12-month-old children in rural Bangladesh. In this 1-year community-based cluster randomized controlled longitudinal experiment, 412 mother-infant pairs were randomly assigned to receive either monthly food vouchers (for eggs, milk, semolina, sugar, and oil) to prepare egg and milk-based snacks for their children, along with multiple micronutrient powder (MNP), counseling on child feeding and handwashing, or regular government health communication alone (control; n = 206, treatment; n = 206). The trial was conducted in 12 clusters (small administrative units of sub-district). The primary inclusion criteria were ultra-poor households with limited resources and having children under 2-years-old. The primary and secondary outcomes were differences in children's length gain and dietary diversity. The effect of intervention on child growth was examined using a mixed effect linear regression model. Mean weight and length of the children did not significantly differ between groups at baseline. Around 90% of the children in both groups were breastfed. After receiving intervention for 12 months, LAZ score increased by 0.37 (CI 0.24, 0.51, p < 0.001) and risk of stunting reduced by 73% (OR: 0.27, CI 0.13, 0.58, p = 0.001). This comprehensive intervention package improved the growth and dietary diversity of children in extremely poor Bangladeshi households. A scaling-up of this intervention in contexts with limited resources should be taken into consideration.Trial registration: This trial registered retrospectively at ClinicalTrials.gov as NCT03641001, 21/8/2018.

Evaluation of outflow temperatures generated by a dry heat fluid warmer at low fluid rates.

OBJECTIVE: To evaluate the output temperature of a dry heat fluid warmer at fluid rates typically used in small animal veterinary patients. STUDY DESIGN: Prospective in vitro study. ANIMALS: None. METHODS: Ambient temperature lactated Ringer's (17.9-18.8 °C) was delivered via a dry heat fluid warmer. A temperature probe was used to measure fluid outflow temperature from the compatible giving set at 5, 10, 20, 50, 70, 80, 100, 200, 300, 400 and 500 mL hour-1. Outflow fluid temperature at plateau (two consecutive readings within 0.1 °C) was compared with baseline fluid temperature (fluid warmer turned off) to calculate temperature changes at each rate. Kruskal-Wallis test was used to compare changes in temperature and time to plateau temperature. Dunn's post hoc test was used to test for significant differences in temperature compared to 5 mL hour-1; p value < 0.05. RESULTS: Median plateau outflow temperature increased as fluid rate increased, with temperatures of 18.5, 18.6, 18.7, 18.8, 19.4, 19.4, 21.5, 25.3, 28.5, 30.7 and 32.6 °C, at flow rates of 5, 10, 20, 50, 70, 80, 100, 200, 300, 400 and 500 mL hour-1. Fluid rates > 100 mL hour-1 showed significant increases from baseline (p = 0.021) There was no difference in temperature change from baseline at fluid rates < 100 mL hour-1 (p > 0.05). Compared to plateau temperature at 5 mL hour-1, there was a statistical difference in plateau temperature above 100 mL hour-1(p = 0.0207). Maximum outflow plateau temperature was 32.6 °C at 500 mL hour-1. CONCLUSIONS AND CLINICAL RELEVANCE: A dry heat fluid warmer has significantly decreased efficacy at low fluid rates, with no statistically significant increase in fluid temperature at fluid rates below 100 mL hour-1 at the end of a compatible fluid line. Inline dry heat fluid warmers are ineffective at fluid rates below 100 mL hour-1.

The impact of working as a peer worker in mental health services: a longitudinal mixed methods study.

BACKGROUND: Peer workers are increasingly employed in mental health services to use their own experiences of mental distress in supporting others with similar experiences. While evidence is emerging of the benefits of peer support for people using services, the impact on peer workers is less clear. There is a lack of research that takes a longitudinal approach to exploring impact on both employment outcomes for peer workers, and their experiences of working in the peer worker role. METHODS: In a longitudinal mixed methods study, 32 peer workers providing peer support for discharge from inpatient to community mental health care - as part of a randomised controlled trial - undertook in-depth qualitative interviews conducted by service user researchers, and completed measures of wellbeing, burnout, job satisfaction and multi-disciplinary team working after completing training, and four and 12 months into the role. Questionnaire data were summarised and compared to outcomes for relevant population norms, and changes in outcomes were analysed using paired t-tests. Thematic analysis and interpretive workshops involving service user researchers were used to analysis interview transcripts. A critical interpretive synthesis approach was used to synthesise analyses of both datasets. RESULTS: For the duration of the study, all questionnaire outcomes were comparable with population norms for health professionals or for the general population. There were small-to-medium decreases in wellbeing and aspects of job satisfaction, and increase in burnout after 4 months, but these changes were largely not maintained at 12 months. Peer workers felt valued, empowered and connected in the role, but could find it challenging to adjust to the demands of the job after initial optimism. Supervision and being part of a standalone peer worker team was supportive, although communication with clinical teams could be improved. CONCLUSIONS: Peer workers seem no more likely to experience negative impacts of working than other healthcare professionals but should be well supported as they settle into post, provided with in-work training and support around job insecurity. Research is needed to optimise working arrangements for peer workers alongside clinical teams.