End of life in haematology: quality of life predictors - retrospective cohort study.

OBJECTIVES: Haematology patients are more likely to receive high intensity care near end of life (EOL) than patients with solid malignancy. Previous authors have suggested indicators of quality EOL for haematology patients, based on a solid oncology model. We conducted a retrospective chart review with the objectives of (1) determining our performance on these quality EOL indicators, (2) describing the timing of level of intervention (LOI) discussion and palliative care (PC) consultation prior to death and (3) evaluating whether goals of therapy (GOT), PC consultation and earlier LOI discussion are predictors of quality EOL. METHODS: We identified patients who died from haematological malignancies between April 2014 and March 2016 (n=319) at four participating McGill University hospitals and performed retrospective chart reviews. RESULTS: We found that 17% of patients were administered chemotherapy less than 14 days prior to death, 20% of patients were admitted to intensive care, 14% were intubated and 5% were resuscitated less than 30 days prior to death, 18% of patients received blood transfusion less than 7 days prior to death and 67% of patients died in an acute care setting. LOI discussion and PC consultation occurred a median of 22 days (IQR 7-103) and 9 days (IQR 3-19) before death. Patients with non-curative GOT, PC consultation or discussed LOI were significantly less likely to have high intensity EOL outcomes. CONCLUSIONS: In this study, we demonstrate that LOI discussions, PC consults and physician established GOT are associated with quality EOL outcomes for patients with haematological malignancies.

B-cell cytopenia and time to last B-cell-depleting therapy predict response to SARS-COV-2 vaccines in patients with lymphoproliferative disorders.

Patients with B-non-Hodgkin lymphoma (NHL) are at increased risk of morbidity and mortality from SARS-CoV-2. We investigated the relationship between B cell cytopenia and the SARS-CoV-2 vaccine response in B-NHL patients. We measured anti-RBD antibodies and the lymphocyte immunophenotype in 19 controls, 22 lymphoma patients on observation (cohort 1) and 55 lymphoma patients receiving their vaccines post B-cell depleting therapy (cohort 2). Half of the lymphoma patients in both cohorts achieved seropositivity compared to 100% of controls. In cohort 2, only 5% achieved an antibody response in the first year post B-cell depleting treatment, vs 88% treated >2 years prior. Also, 28% of patients with <50 B cells/µl achieved a serologic response vs 86% of patients with B-cell >50 B cells/µl. B-cell cytopenia is profound within the first year of exposure to B-cell depleting treatment, therefore an additional dose of vaccine within that timeframe is unlikely to raise antibody levels.

The hyperinsulinemic amino acid clamp increases whole-body protein synthesis in young subjects.

We propose that hyperinsulinemia stimulates protein synthesis when postabsorptive plasma amino acid (AA) concentrations are maintained. During a euglycemic hyperinsulinemic clamp, many AA, notably the branched-chain amino acids (BCAA), decline markedly. Therefore, we tested whether individual plasma AA could be maintained within the range of postabsorptive concentrations to assess the effects of insulin, infused at 40 mU/m(2) x min on whole-body protein and glucose metabolism, using [1-(13)C]-leucine and [3-(3)H]-glucose methodology. Validation studies of background [(13)C] enrichment and breath (13)CO(2) recovery factors were performed in a subset of 6 subjects. In 10 healthy, young men, infusion rates of an AA solution were based on fluorometric determinations of total BCAA every 5 minutes. All 21 plasma AA remained in the target range; 15, including the BCAA, alanine, and glycine were within 13% of baseline, and only 6 (Thr, His, Arg, Asn, Cit, Tyr) varied more (18% to 42%). Notably, both leucine flux and nonoxidative leucine R(d) (protein synthesis) increased with insulin (2.36 +/- 0.06 to 2.81 +/- 0.10 and 1.79 +/- 0.05 to 2.18 +/- 0.10 micromol/kg fat-free mass (FFM) x min, respectively; P <.0005) while leucine oxidation only tended to increase (P =.05) and endogenous leucine R(a) (protein breakdown) decreased by 18% (2.36 +/- 0.06 to 1.94 +/- 0.09 micromol/kg FFM x min; P <.0005), resulting in a marked elevation of net protein synthesis (-0.57 +/- 0.02 to 0.24 +/- 0.02 micromol/kg FFM x min; P <.0000001). Thus, in vivo protein anabolism was induced when maintaining postabsorptive plasma amino acid concentrations during hyperinsulinemia through a suppression of whole-body protein breakdown, no significant change in oxidation and an elevation of synthesis compared with postabsorptive conditions.