Immune responses to COVID-19 booster vaccinations in intensively anti-CD38 antibody treated patients with ultra-high-risk multiple myeloma: results from the Myeloma UK (MUK) nine OPTIMUM trial

Multiple myeloma (MM) and anti-MM therapy cause profound immunosuppression, leaving patients vulnerable to coronavirus disease 2019 (COVID-19) and other infections. We investigated anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies longitudinally in ultra-high-risk patients with MM receiving risk-adapted, intensive anti-CD38 combined therapy in the Myeloma UK (MUK) nine trial. Despite continuous intensive therapy, seroconversion was achieved in all patients, but required a greater number of vaccinations compared to healthy individuals, highlighting the importance of booster vaccinations in this population. Reassuringly, high antibody cross-reactivity was found with current variants of concern, prior to Omicron subvariant adapted boostering. Multiple booster vaccine doses can provide effective protection from COVID-19, even with intensive anti-CD38 therapy for high-risk MM.     

@ease peer-to-peer youth walk-in centres in The Netherlands: A protocol for evaluating longitudinal outcomes,follow-up results and cost-of-illness

Aim

Innovative youth mental health services around the globe vigorously work on increasing highly needed mental health care accessibility but their service users and care effectiveness have rarely been studied. The Dutch youth walk-in centres of @ease opened in 2018, with currently 11 locations at which free anonymous peer-to-peer counselling is offered to young people aged 12–25. The aim of this protocol is to outline the to-be-conducted research at @ease.

Methods

Three studies are outlined: (1) an outcome evaluation of @ease visits using hierarchical mixed model analyses and change calculations, (2) a cost-of-illness study using calculations for costs of truancy and care usage among these help-seeking young people, with regression analyses for risk group identification, and (3) a follow-up evaluation at three, six and 12 months to assess long-term effects after ending @ease visits. Data provided by young people include demographics, parental mental illness, truancy, past treatment, psychological distress (CORE-10) and health-related quality of life (EQ-5D-5L). Social and occupational functioning (SOFAS), suicidal ideation and need for referral are rated by the counsellors. Questionnaires are filled out at the end of every visit and at follow-up via e-mail or text, provided permission is given.

Discussion

Research regarding the visitors and effectiveness of the @ease services is fully original. It offers unique insights into the mental wellbeing and cost-of-illness of young people who may otherwise remain unseen while suffering from a high disease burden. The upcoming studies shed light on this unseen group, inform policy and practice and direct future research.     

Hypoglycaemia induces a sustained pro-inflammatory response in people with type 1 diabetes and healthy controls

Aim

To determine the duration and the extension of the pro-inflammatory response to hypoglycaemia both in people with type 1 diabetes and healthy controls.

Materials and Methods

Adults with type 1 diabetes (n = 47) and matched controls (n = 16) underwent a hyperinsulinaemic-euglycaemic hypoglycaemic (2.8 ± 0.1 mmoL/L [49.9 ± 2.3 mg/dL]) glucose clamp. During euglycaemia, hypoglycaemia, and 1, 3 and 7 days later, blood was drawn to determine immune cell phenotype, monocyte function and circulating inflammatory markers.

Results

Hypoglycaemia increased lymphocyte and monocyte counts, which remained elevated for 1 week. The proportion of CD16⁺ monocytes increased and the proportion of CD14⁺ monocytes decreased. During hypoglycaemia, monocytes released more tumour necrosis factor-α and interleukin-1β, and less interleukin-10, after ex vivo stimulation. Hypoglycaemia increased the levels of 19 circulating inflammatory proteins, including high sensitive C-reactive protein, most of which remained elevated for 1 week. The epinephrine peak in response to hypoglycaemia was positively correlated with immune cell number and phenotype, but not with the proteomic response.

Conclusions

Overall, despite differences in prior exposure to hypoglycaemia, the pattern of the inflammatory responses to hypoglycaemia did not differ between people with type 1 diabetes and healthy controls. In conclusion, hypoglycaemia induces a range of pro-inflammatory responses that are sustained for at least 1 week in people with type 1 diabetes and healthy controls.