ABSTRACT
Background: Most people would rather die at home than in hospital but only 18% of patients do so. Palliative care focuses on the physical, spiritual and psychosocial wellbeing of patients and their families, which should include facilitating transfers home when possible. Patients can have more autonomy over their care and be surrounded by loved ones which can have a significant impact on their quality of life. In this article we describe two cases of home repatriation for palliation. Case 1 describes the transfer of a patient with difficulties and gaps in planning, but with a safe transfer ultimately. Case 2 recounts a more comprehensive planning process emphasising collaboration between teams. Benefits and difficulties of palliative critical care transfers: Facilitating home-based care aligns with patients' desires for familiar surroundings and emotional support. A secondary benefit is that releasing a bed space allows another patient to receive critical care treatment. Challenges of palliative critical care transfers include needing a highly trained team and thorough planning. Early discussion with the family and community palliative care teams makes this a more feasible option for patients. Conclusion: A multidisciplinary team of hospital and community healthcare professionals working with the patient and their family can facilitate the transfer from intensive care to allow them to die at a place of their choosing. We should aim to fulfil these wishes at the end of life as it can greatly improve the patient's and their family's physical and emotional wellbeing during this difficult time.
ABSTRACT
Patients with familial platelet disorder with a predisposition to myeloid malignancy (FPDMM) harbor germline monoallelic mutations in a key hematopoietic transcription factor, RUNX-1. Previous studies of FPDMM have focused on megakaryocyte (Mk) differentiation and platelet production and signaling. However, the effects of RUNX-1 haploinsufficiency on hematopoietic progenitor cells (HPCs) and subsequent megakaryopoiesis remains incomplete. We studied induced pluripotent stem cell (iPSC)-derived HPCs (iHPCs) and Mks (iMks) from both patient-derived lines and a wild-type (WT) line modified to be RUNX-1 haploinsufficient (RUNX-1+/-), each compared with their isogenic WT control. All RUNX-1+/- lines showed decreased iMk yield and depletion of an Mk-biased iHPC subpopulation. To investigate global and local gene expression changes underlying this iHPC shift, single-cell RNA sequencing was performed on sorted FPDMM and control iHPCs. We defined several cell subpopulations in the Mk-biased iHPCs. Analyses of gene sets upregulated in FPDMM iHPCs indicated enrichment for response to stress, regulation of signal transduction, and immune signaling-related gene sets. Immunoblot analyses in FPDMM iMks were consistent with these findings, but also identified augmented baseline c-Jun N-terminal kinase (JNK) phosphorylation, known to be activated by transforming growth factor-ß1 (TGF-ß1) and cellular stressors. These findings were confirmed in adult human CD34+-derived stem and progenitor cells (HSPCs) transduced with lentiviral RUNX1 short hairpin RNA to mimic RUNX-1+/-. In both iHPCs and CD34+-derived HSPCs, targeted inhibitors of JNK and TGF-ß1 pathways corrected the megakaryopoietic defect. We propose that such intervention may correct the thrombocytopenia in patients with FPDMM.
