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Immune-related adverse events: a retrospective look into the future of oncology in the intensive care unit.

ABSTRACT: BACKGROUND:Immune checkpoint inhibitors have reshaped the standard of care in oncology. However, they have been associated with potentially life-threatening immune-related adverse events. With the growing indications of immune checkpoint inhibitors and their position as a pillar of cancer treatment, intensive care physicians will be increasingly confronted with their side effects. The outcome of patients with severe immune-related adverse events in the intensive care unit remains unknown. This retrospective multicentric study aims to describe the characteristics of patients admitted to the intensive care units of 4 academic hospitals in Paris area while receiving immune checkpoint inhibitor treatment between January 2013 and October 2019. RESULTS:Over the study period, 112 cancer patients who received immune checkpoint inhibitors were admitted to the intensive care unit within 60 days after the last dose. ICU admission was related to immune-related adverse events (n?=?29, 26%), other intercurrent events (n?=?39, 35%), or complications related to tumor progression (n?=?44, 39%). Immune-related adverse events were pneumonitis (n?=?8), colitis (n?=?4), myocarditis (n?=?3), metabolic disorders related to diabetes (n?=?3), hypophysitis (n?=?2), nephritis (n?=?2), meningitis or encephalitis (n?=?2), hepatitis (n?=?2), anaphylaxis (n?=?2) and pericarditis (n?=?1). Primary tumors were mostly melanomas (n?=?14, 48%), non-small-cell lung cancers (n?=?7, 24%), and urothelial carcinomas (n?=?5, 17%). Diagnosis of melanoma and a neutrophil/lymphocyte ratio?

SUBMITTER: Joseph A

PROVIDER: S-EPMC7567777 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Immune-related adverse events: a retrospective look into the future of oncology in the intensive care unit.

Joseph Adrien A Simonaggio Audrey A Stoclin Annabelle A Vieillard-Baron Antoine A Geri Guillaume G Oudard Stéphane S Michot Jean-Marie JM Lambotte Olivier O Azoulay Elie E Lemiale Virginie V

Annals of intensive care 20201016 1

<h4>Background</h4>Immune checkpoint inhibitors have reshaped the standard of care in oncology. However, they have been associated with potentially life-threatening immune-related adverse events. With the growing indications of immune checkpoint inhibitors and their position as a pillar of cancer treatment, intensive care physicians will be increasingly confronted with their side effects. The outcome of patients with severe immune-related adverse events in the intensive care unit remains unknown ...[more]

PMID: 33064239

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Project description:Critically ill intensive care unit (ICU) patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decrease quality of life of survivors. Acute Quadriplegic Myopathy (AQM) is one of the most common neuromuscular disorders associated with ICU-acquired muscle weakness. Although there are no available treatments for the ICU-acquired muscle weakness, it has been demonstrated that early mobilization can improve its prognosis and functional outcomes. This study aims at improving our understanding of the effects of passive mechanical loading on skeletal muscle structure and function by using a unique experimental rat ICU model allowing analyses of the temporal sequence of changes in mechanically ventilated and pharmacologically paralyzed animals at durations varying from 6 h to 14 days. Results show that passive mechanical loading alleviated the muscle wasting and the loss of force-generation associated with the ICU intervention, resulting in a doubling of the functional capacity of the loaded vs. unloaded muscles after a 2-week ICU intervention. We demonstrated that the improved maintenance of muscle structure and function is likely a consequence of a reduced oxidative stress, and a reduced loss of the molecular motor protein myosin. A complex temporal gene expression pattern, delineated by microarray analysis, was observed with loading-induced changes in transcript levels of sarcomeric proteins, muscle developmental processes, stress response, ECM/cell adhesion proteins and metabolism. Thus, the results from this study show that passive mechanical loading alleviates the severe negative consequences on muscle structure and function associated with mechanical silencing in ICU patients, strongly supporting early and intense physical therapy in immobilized ICU patients. This study aims to unravel the effects of passive mechanical loading on skeletal muscle structure and function in an experimental rat ICU model at duration varying between 6h and 14 days. A total of 23 experimental female Sprague-Dawley rats were included in this study. The experimental rats were anaesthetized, treated with the neuromuscular blocking agent (NMBA) M-NM-1-cobrotoxin, mechanically ventilated and monitored for durations varying from 6h to 4 days (n=13), from 5 to 8 days (n=4), and from 9 to 14 days (n=6). The left leg of the animal was activated for 6 hours at the shortest duration and 12 hours per day at durations 12 hours and longer throughout the experiment, using a mechanical lever arm that produced a continuous passive maximal ankle joint flexions-extensions at a speed of 13.3 cycles per minute. Muscle biopsies were obtained from gastrocnemius muscle (proximal part) immediately after euthanasia, were quickly frozen in liquid propane cooled by liquid nitrogen, and stored at -80M-BM-0C. RNA was extracted.

Dataset Information

Immune-related adverse events: a retrospective look into the future of oncology in the intensive care unit.

Publications

Immune-related adverse events: a retrospective look into the future of oncology in the intensive care unit.

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