5 research outputs found
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Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma
Abstract: The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy
Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study
Purpose:
Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom.
Methods:
Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded.
Results:
The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia.
Conclusion:
We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes
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Clinical and economic impact of the introduction of pre-biopsy MRI-based assessment on a large prostate cancer centre diagnostic population and activity: 10Â years on.
INTRODUCTION: Prostate mpMRI was introduced in 2011 as a secondary test and subsequently integrated into a prostate cancer (PCa) diagnostics unit representing a population of approximately 550,000 people. The following represents an audit of its step-wise introduction between 2 index years, 2009 and 2018, focusing on the activity, patient outcomes and economic benefits. PATIENTS AND METHODS: The 2 distinct years were selected for relying on a transrectal ultrasound biopsy pathway in 2009 to an mpMRI-based pathway in 2018. All referrals were retrospectively screened and compared for age, PSA levels, DRE findings, biopsy history, biopsy and mpMRI allocation data. Cost analysis was determined using local unit procedure costs. RESULTS: Patients referred included 648 in 2009 and 714 in 2018. mpMRI seldomly informed decision to biopsy in 2009 (9.8%), while in 2018 it was performed in the pre-biopsy setting in 87.9% cases and enabled biopsy avoidance in 137 patients. In 2018, there was a 31.8% decrease in the number of biopsies in patients without previous PCa diagnosis, coupled with an increase in diagnostic rates of csPCa, from 28.6 to 49.0% (p < 0.0001) and a reduction in negative biopsy rates from 52.3 to 33.8%. mpMRI had a positive impact on the system with reduced patient morbidity and post-procedural complications. The estimated overall cost savings amount to approximately £75,000/year for PCa diagnosis and £11,000/year due to reduced complications. CONCLUSION: Our evaluation shows the mpMRI-based pathway has improved early detection of csPCa and reduction of repeat biopsies, resulting in significant financial benefits for the local healthcare system