Long-term Host Immune Response Trajectories Among Hospitalized Patients With Sepsis

Yende, Sachin; Kellum, John A.; Talisa, Victor B.; Palmer, Octavia M. Peck; Chang, Chung‐Chou H.; Filbin, Michael R.; Shapiro, Nathan I.; Hou, Peter C.; Venkat, Arvind; LoVecchio, Frank; Hawkins, Katrina; Crouser, Elliott D.; Newman, Anne B.; Angus, Derek C.

doi:10.1001/jamanetworkopen.2019.8686

Cited by 112 publications

(120 citation statements)

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“…The 1-year mortality rate among sepsis survivors in the present study is within the range previously reported in the literature. 9,16,36 Shankar-Hari et al 16 and Yende et al 36 recently reported 1-year mortality rates of 15% and 17.6%, respectively, among relatively young and previously healthy patients with few comorbidities and high rates of prehospital functional independence. In contrast,…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Long-term Mortality and Patterns of End-of-Life Care Among Medicare Sepsis Survivors Discharged to Home Health Care

et al. 2020

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IMPORTANCE Despite a growing recognition of the increased mortality risk among sepsis survivors, little is known about the patterns of end-of-life care among this population. OBJECTIVE To describe patterns of end-of-life care among a national sample of sepsis survivors and identify factors associated with long-term mortality risk and hospice use. DESIGN, SETTING, AND PARTICIPANTS This cohort study assessed sepsis survivors who were Medicare fee-for-service beneficiaries discharged to home health care using national Medicare administrative, claims, and home health assessment data from 2013 to 2014. The initial and final primary analyses were conducted in July 2017 and from July to August 2019, respectively. EXPOSURES Sepsis hospital discharge and 1 or more home health assessments within 1 week. MAIN OUTCOMES AND MEASURES Outcomes were 1-year mortality among all sepsis survivors and hospitalization in the last 30 days of life, death in an acute care hospital, and hospice use among decedents. Multivariate logistic regression was used to identify factors associated with 1-year mortality and hospice use. RESULTS Among 87 581 sepsis survivors who were Medicare fee-for-service beneficiaries discharged to home health care, 49 323 (56.3%) were aged 75 years or older, 69 499 (79.4%) were non-Hispanic white, and 48 472 (55.3%) were female. Among the total survivors, 24 423 (27.9%) people died within 1 year of discharge, with a median (interquartile range) survival time of 119 (51-220) days. Among these decedents, 16 684 (68.2%) were hospitalized in the last 30 days of life, 6560 (26.8%) died in an acute care hospital, and 12 573 (51.4%) were enrolled in hospice, with 5729 (45.6%) using hospice for 7 or fewer days. Several factors were associated with 1-year mortality, including a cancer diagnosis (odds ratio [OR], 3.66; 95% CI, 3.50-3.83; P < .001), multiple dependencies of activities of daily living or instrumental activities of daily living (OR, 2.80; 95% CI, 2.57-3.05; P < .001), and an overall poor health status (OR, 2.21; 95% CI, 2.01-2.44; P < .001) documented on home health assessment. Among the decedents, cancer was associated with hospice use (OR, 2.25; 95% CI, 2.11-2.41; P < .001), patients aged 85 years or older (OR, 1.49; 95% CI, 1.37-1.61; P < .001), and living in an assisted living setting (OR, 1.93; 95% CI, 1.69-2.19; P < .001). CONCLUSIONS AND RELEVANCE The findings of this study suggest that death within 1 year after sepsis discharge may be common among Medicare beneficiaries discharged to home health care. Although 1 in 2 decedents used hospice, aggressive care near the end of life and late hospice referral were common. Readily identifiable risk factors suggest opportunities to target efforts to improve palliative and end-of-life care among high-risk sepsis survivors.

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Section: Discussionmentioning

confidence: 99%

Risk Factors for Long-term Mortality and Patterns of End-of-Life Care Among Medicare Sepsis Survivors Discharged to Home Health Care

et al. 2020

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“…We and others have highlighted that 1 in 2 sepsis survivors have unplanned rehospitalizations or die in the first year after hospital discharge. 19 , 29 , 30 , 31 Currently, the follow-up care of sepsis survivors is neither risk based nor uniform within and between health care systems. Seldom does every sepsis survivor receive follow-up care.…”

Section: Discussionmentioning

confidence: 99%

Development, Validation, and Clinical Utility Assessment of a Prognostic Score for 1-Year Unplanned Rehospitalization or Death of Adult Sepsis Survivors

et al. 2020

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Key Points Question Could a prognostic score for unplanned rehospitalizations or death in the first year after hospital discharge of adult sepsis survivors be developed using index sepsis illness characteristics as predictors? Findings In this cohort study of 94 748 patients in adult general critical care units in England, unplanned rehospitalization or death in the first year after hospital discharge occurred for 51% of patients in the derivation cohort and 53% of patients in the validation cohort. The prognostic score is calculated using 8 predictors: previous hospitalizations in the preceding year, age, socioeconomic status, preadmission dependence, number of comorbidities, admission type, site of infection, and admission blood hemoglobin level. Meaning This score provides clinically useful information for prognosis discussions and planning follow-up care for sepsis survivors.

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“…In hospital survivors, failure to achieve homeostatic correction has a significant negative long-term impact, with experimental work suggesting that it might potentiate the peripheral and brain pro-inflammatory cytokine response to a subsequent inflammatory challenge (44). Independently of age and comorbidities, patients with elevated circulating biomarkers of inflammation and hemostasis at hospital discharge have persistent elevation over time with increased risk for cardiovascular events, re-hospitalizations, and 1-year mortality (41,45,46). "Persistent Inflammation, Immunosuppression, and Catabolism Syndrome" (PICS) has been postulated as the underlying pathophysiology of chronic critical illness (CCI) (18,47).…”

Section: Innate Immunity and Nuclear Factor-κbmentioning

confidence: 99%

General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections

Meduri

Chrousos

2020

Front. Endocrinol.

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In critical illness, homeostatic corrections representing the culmination of hundreds of millions of years of evolution, are modulated by the activated glucocorticoid receptor alpha (GRα) and are associated with an enormous bioenergetic and metabolic cost. Appreciation of how homeostatic corrections work and how they evolved provides a conceptual framework to understand the complex pathobiology of critical illness. Emerging literature place the activated GRα at the center of all phases of disease development and resolution, including activation and re-enforcement of innate immunity, downregulation of pro-inflammatory transcription factors, and restoration of anatomy and function. By the time critically ill patients necessitate vital organ support for survival, they have reached near exhaustion or exhaustion of neuroendocrine homeostatic compensation, cell bio-energetic and adaptation functions, and reserves of vital micronutrients. We review how critical illness-related corticosteroid insufficiency, mitochondrial dysfunction/damage, and hypovitaminosis collectively interact to accelerate an anti-homeostatic active process of natural selection. Importantly, the allostatic overload imposed by these homeostatic corrections impacts negatively on both acute and long-term morbidity and mortality. Since the bioenergetic and metabolic reserves to support homeostatic corrections are time-limited, early interventions should be directed at increasing GRα and mitochondria number and function. Present understanding of the activated GC-GRα's role in immunomodulation and disease resolution should be taken into account when re-evaluating how to administer glucocorticoid treatment and co-interventions to improve cellular responsiveness. The activated GRα interdependence with functional mitochondria and three vitamin reserves (B1, C, and D) provides a rationale for co-interventions that include prolonged glucocorticoid treatment in association with rapid correction of hypovitaminosis.

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Long-term Host Immune Response Trajectories Among Hospitalized Patients With Sepsis

Abstract: This multicenter cohort study of adults who have survived hospitalization for sepsis assesses whether abnormalities in the host immune response during hospitalization for sepsis persist after discharge.

Cited by 112 publications

References 20 publications

Risk Factors for Long-term Mortality and Patterns of End-of-Life Care Among Medicare Sepsis Survivors Discharged to Home Health Care

Risk Factors for Long-term Mortality and Patterns of End-of-Life Care Among Medicare Sepsis Survivors Discharged to Home Health Care

Development, Validation, and Clinical Utility Assessment of a Prognostic Score for 1-Year Unplanned Rehospitalization or Death of Adult Sepsis Survivors

General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections

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