A multicentre prospective audit of bedside hydration in hospital.

INTRODUCTION: access to water at the bedside is a cornerstone of patient care. Among bedbound inpatients, water within reach at the bedside is a basic human dignity and one that ought not to be neglected. AIM: the authors sought to identify the extent to which accessible hydration facilities were provided to a bedbound inpatient population. METHODS: a cross-sectional, point-prevalent audit of hospitalised medical inpatients across five centres was conducted. Data were collected between meal times and noted baseline demographics and admission details, adequacy of oral hydration provision at the bedside and, where provision was inadequate, factors associated with this. RESULTS: across a total surveyed patient population of 559 we identified 138 patients who were bedbound. Among these bedbound patients, 6% (n=8) had no water provided at the bedside. However, 7 of these were deemed to be unable to swallow safely. In total, 44 (32%) of the 138 bedbound patients were unable to reach the water at their bedside; 18 of these patients would have been able to drink for themselves had the water been in reach. CONCLUSION: there is significant room for improvement in ensuring patients who are immobile are able to reach drinking apparatus at the bedside. In the five centres surveyed, approximately one in five bedbound patients with no contraindication are unable to reach an essential means of hydration.

Disease evolution and outcomes in familial AML with germline CEBPA mutations.

In-depth molecular investigation of familial leukemia has been limited by the rarity of recognized cases. This study examines the genetic events initiating leukemia and details the clinical progression of disease across multiple families harboring germ-line CEBPA mutations. Clinical data were collected from 10 CEBPA-mutated families, representing 24 members with acute myeloid leukemia (AML). Whole-exome (WES) and deep sequencing were performed to genetically profile tumors and define patterns of clonal evolution. Germline CEBPA mutations clustered within the N-terminal and were highly penetrant, with AML presenting at a median age of 24.5 years (range, 1.75-46 years). In all diagnostic tumors tested (n = 18), double CEBPA mutations (CEBPAdm) were detected, with acquired (somatic) mutations preferentially targeting the C-terminal. Somatic CEBPA mutations were unstable throughout the disease course, with different mutations identified at recurrence. Deep sequencing of diagnostic and relapse paired samples confirmed that relapse-associated CEBPA mutations were absent at diagnosis, suggesting recurrence was triggered by novel, independent clones. Integrated WES and deep sequencing subsequently revealed an entirely new complement of mutations at relapse, verifying the presentation of a de novo leukemic episode. The cumulative incidence of relapse in familial AML was 56% at 10 years (n = 11), and 3 patients experienced ≥3 disease episodes over a period of 17 to 20 years. Durable responses to secondary therapies were observed, with prolonged median survival after relapse (8 years) and long-term overall survival (10-year overall survival, 67%). Our data reveal that familial CEBPA-mutated AML exhibits a unique model of disease progression, associated with favorable long-term outcomes.

Dismantling of cadherin-mediated cell-cell contacts modulates smooth muscle cell proliferation.

Proliferation of vascular smooth muscle cells (VSMCs) contributes to intimal thickening during atherosclerosis and restenosis. The cadherins are transmembrane proteins, which form cell-cell contacts and may regulate VSMC proliferation. In this study, N-cadherin protein concentration was significantly reduced by stimulation of proliferation with fetal calf serum (FCS) and platelet-derived growth factor-BB (PDGF-BB) in human saphenous vein VSMCs. Furthermore, overexpression of a truncated N-cadherin, which acts as a dominant-negative increased VSMC proliferation. The amount of an extracellular fragment of N-cadherin (approximately 90 kDa) in the media after 24 hours was increased by 12-fold by FCS and 11-fold by PDGF-BB, suggesting that N-cadherin levels are regulated by proteolytic shedding. Incubation with a synthetic metalloproteinase inhibitor or adenoviral overexpression of the endogenous tissue inhibitors of metalloproteinases (TIMPs) demonstrated that metalloproteinase activity was responsible in part for this proteolysis. Although total levels of beta-catenin protein were not affected, beta-catenin was translocated to the nucleus after stimulation with FCS and PDGF-BB. Our data indicates cadherin-mediated cell-cell contacts modulate proliferation in VSMCs. Furthermore, disruption of N-cadherin cell-cell contacts mediated in part by metalloproteinase activity occurs during VSMC proliferation, releasing beta-catenin and possibly inducing beta-catenin-mediated intracellular signaling.