Investigating the utility of saliva immunoglobulins for the detection of myeloma and using myeloma proteins to clarify partition between oral and systemic immunity.

OBJECTIVES: Myeloma is characterised by the presence of monoclonal immunoglobulin (M-protein) and the free light chain (FLC) in blood. We investigated whether these M-proteins and FLC are detectable in myeloma patients' saliva to evaluate its utility for non-invasive screening and monitoring of haematological malignancies. METHODS: A total of 57 patients with monoclonal gammopathy and 26 age-matched healthy participants provided paired serum and saliva samples for immunoglobulin characterisation and quantification. RESULTS: Myeloma patients had IgG or IgA M-protein levels ranging up to five times and FLC levels up to a thousand times normal levels of polyclonal immunoglobulins. Despite these highly elevated levels, only two IgG and no IgA M-proteins or FLC could be detected in paired saliva samples. Most patients had reduced levels of serum polyclonal immunoglobulins, but all had normal levels of salivary IgA. CONCLUSIONS: Immunoglobulin transfer from blood is not determined by levels in the systemic circulation and more likely dictated by periodontal inflammation and the integrity of the oral epithelium. Immunoglobulins secreted by bone marrow plasma cells do not substantially enter saliva, which represents a poor medium for myeloma diagnosis. These findings, along with normal salivary IgA levels despite systemic immunoparesis, support a strong partitioning of oral from systemic humoral immunity.

Free light chains as an emerging biomarker in saliva: Biological variability and comparisons with salivary IgA and steroid hormones.

BACKGROUND: Salivary free light chains (FLCs) are an emerging biomarker in health and behavioural research. However, little is known regarding biological variability of salivary FLCs and how they relate to other established salivary biomarkers. This study aimed to investigate the diurnal and day-to-day variation of salivary FLCs and their relationship with salivary IgA and steroid hormones. METHODS: A total of 46 healthy adults participated in studies exploring the biological variability of FLCs. Diurnal variation was investigated by collecting saliva samples immediately upon waking, 0.5 h, 3 h, 6 h, 9 h and 14 h post-waking. Saliva samples were assessed for FLCs, IgA, cortisol and dehydroepiandrosterone (DHEA). Between-day variation in FLCs and IgA was assessed by collecting saliva samples immediately upon waking for seven consecutive days. Participants underwent a dental examination to exclude oral health as a potential confounding variable. Within and between-person day-to day variation was explored in relation to a range of different factors: awakening time, sleep, exercise, well-being and alcohol consumption. RESULTS: Salivary secretion rates of FLCs decreased following waking and up to 3 h post-waking and then plateaued. This same pattern was observed for IgA. DHEA was stable upon waking and higher levels were seen in the morning with significantly lower levels thereafter. Cortisol levels significantly increased 0.5 h post-waking then continued to decline across the day. FLCs were significantly correlated with IgA but not cortisol or DHEA. Both FLCs and IgA parameters showed day-to-day variability, with coefficients of variation ≥ 40%. Earlier waking time was significantly correlated with higher FLC and IgA secretion rates. Inter-person differences in saliva parameter variability were observed but the degree of variation in FLCs and IgA was related within person. Inter-person day-to-day variation appeared to be uninfluenced by lifestyle or behavioural factors. CONCLUSIONS: Saliva FLCs secretion exhibits diurnal fluctuation that mirrors IgA fluctuation. Findings strongly indicate salivary FLC secretion is orchestrated by local plasma cells. FLCs and IgA both showed notable variability day-to-day, which was similar within person and influenced by awakening time. FLCs offer a promising adjunct to IgA in the measurement of oral immune activation.

Exploring Medical Student Attitudes Regarding Inter-university Learning: A Pilot Study.

Introduction The United Kingdom needs to educate more medical students to meet workforce demands. With static numbers of clinical teachers available, novel and efficient approaches are required to prepare students for real-life work where doctors routinely work with colleagues from different medical schools. This innovative project was designed to investigate student attitudes towards inter-university learning (IUL), whereby two medical students from different universities learn together. Materials and methods Thirteen students at Great Western Hospital, Swindon, England, volunteered and were randomly paired with a student from another university. Pairs completed a 20-minute simulated clinical scenario and observed three others. Students completed pre- and post-session questionnaires adapted from the Readiness for Inter-Professional Learning scale. Seven students took part in semi-structured interviews which underwent thematic analysis. Results Quantitative analysis of post-session questionnaires demonstrated a positive response to IUL. Thematic analysis generated six themes: impact on learning, impact on career, working together, recognising differences, practical considerations, and psychosocial perspectives. Discussion Students enjoyed the social learning opportunity to practise team-working, communication, and role delegation with unknown peers whilst sharing different clinical approaches. Differences in course structure meant students displayed varying strengths, although unexpected findings centred around pre-conceptions of both universities and social comparison behaviours. Conclusion IUL's strength was deemed to be in non-technical skill development to prepare for real-life work, ultimately enhancing patient safety. Practicalities to consider include session design and psychological safety. IUL provides a novel solution to efficiently educate future healthcare professionals and further work to explore its benefits on a wider scale is suggested.

Improving the visibility and communication of treatment escalation plans in Somerset NHS foundation trust.

BACKGROUND: Advance care treatment escalation plans (TEPs) are often lost between healthcare settings, leading to duplication of work and loss of patient autonomy. OBJECTIVE: This quality improvement project reviewed the usage of TEP forms and aimed to improve completeness of documentation and visibility between admissions. METHODS: Over four months we monitored TEP form documentation using a standardised data extraction form. This examined section completion, seniority of documenting clinician and transfer of forms to our hospital electronic patient record (EPRO). We added reminders to computer monitors on wards to improve EPRO upload. RESULTS: Initial data demonstrated that 95% of patients (n = 230) had a TEP, with 99% of TEPs recording resuscitation status. However, other sections were not well documented (patient capacity 57% completion and personal priorities 45% completion, respectively). Only 11.9% of TEPs documented consultant involvement. Furthermore, only 44% of TEPs with a do not attempt resuscitation (DNACPR) decision were uploaded. Following this, we added reminders to computer monitors explaining how to upload TEP decisions to EPRO, which increased EPRO uploads to 74%. CONCLUSION: Communication of TEPs needs improving across healthcare settings. This project showed that the use of a physical reminder can greatly improve communication of treatment escalation decisions. Furthermore, this intervention has inspired future projects aiming at making communication more sustainable through the use of discharge summaries.