Older adults demonstrate biomarker evidence of the persistent inflammation, immunosuppression and catabolism syndrome (PICS) after sepsis.

BACKGROUND Hospital deaths after sepsis have decreased substantially and most young adult survivors rapidly recover (RAP). However, many older survivors develop chronic critical illness (CCI) with poor long-term outcomes. The etiology of CCI is multifactorial and the relative importance remains unclear. Sepsis is caused by a dysregulated immune response and biomarkers reflecting a persistent inflammation, immunosuppression and catabolism syndrome (PICS) have been observed in CCI after sepsis. Therefore, the purpose of this study was to compare serial PICS biomarkers in a) older (versus young) adults and b) older CCI (versus older RAP) patients to gain insight into underlying pathobiology of CCI in older adults. METHODS Prospective longitudinal study with young (≤ 45 years) and older (≥ 65 years) septic adults who were characterized by a) baseline predisposition, b) hospital outcomes, c) serial SOFA organ dysfunction scores over 14 days, d) Zubrod Performance status at three, six and 12-month follow-up and e) mortality over 12 months. Serial blood samples over 14 days were analyzed for selected biomarkers reflecting PICS. RESULTS Compared to the young, more older adults developed CCI (20% vs 42%) and had markedly worse serial SOFA scores, performance status and mortality over 12 months. Additionally, older (versus young) and older CCI (versus older RAP) patients had more persistent aberrations in biomarkers reflecting inflammation, immunosuppression, stress metabolism, lack of anabolism and anti-angiogenesis over 14 days after sepsis. CONCLUSION Older (versus young) and older CCI (versus older RAP) patient subgroups demonstrate early biomarker evidence of the underlying pathobiology of PICS.

[1]  A. Salminen Increased immunosuppression impairs tissue homeostasis with aging and age-related diseases , 2020, Journal of molecular medicine.

[2]  H. Crossland,et al.  Glucagon‐like peptide 1 infusions overcome anabolic resistance to feeding in older human muscle , 2020, Aging cell.

[3]  B. Brumback,et al.  Phenotypic heterogeneity by site of infection in surgical sepsis: a prospective longitudinal study , 2020, Critical Care.

[4]  B. Brumback,et al.  Older Sepsis Survivors Suffer Persistent Disability Burden and Poor Long-Term Survival , 2020, Journal of the American Geriatrics Society.

[5]  F. Moore,et al.  Chronic Critical Illness Patients Fail to Respond to Current Evidence-Based Intensive Care Nutrition Secondarily to Persistent Inflammation, Immunosuppression, and Catabolic Syndrome. , 2020, JPEN. Journal of parenteral and enteral nutrition.

[6]  Nikolas I. Krieger,et al.  Association of Lymphopenia With Risk of Mortality Among Adults in the US General Population , 2019, JAMA network open.

[7]  Marie-Pierre L. Gauthier,et al.  Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis , 2019, Critical Care.

[8]  R. Hotchkiss,et al.  IL-10 Has Differential Effects on the Innate and Adaptive Immune Systems of Septic Patients , 2019, The Journal of Immunology.

[9]  S. Anton,et al.  Current Epidemiology of Surgical Sepsis: Discordance Between Inpatient Mortality and 1-Year Outcomes. , 2019, Annals of surgery.

[10]  Octavia M Peck Palmer,et al.  Long-term Host Immune Response Trajectories Among Hospitalized Patients With Sepsis , 2019, JAMA network open.

[11]  L. Moldawer,et al.  Persistently Elevated Glucagon-Like Peptide-1 Levels among Critically Ill Surgical Patients after Sepsis and Development of Chronic Critical Illness and Dismal Long-Term Outcomes. , 2019, Journal of the American College of Surgeons.

[12]  M. Rapoport,et al.  Sepsis‐induced activation of endogenous GLP‐1 system is enhanced in type 2 diabetes , 2018, Diabetes/metabolism research and reviews.

[13]  H. Ueno,et al.  Innate Immunity in the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome and Its Implications for Therapy , 2018, Front. Immunol..

[14]  Derek C. Angus,et al.  Enhancing Recovery From Sepsis: A Review , 2018, JAMA.

[15]  B. Brumback,et al.  Evidence for Persistent Immune Suppression in Patients Who Develop Chronic Critical Illness After Sepsis , 2017, Shock.

[16]  B. Brumback,et al.  Sepsis and Critical Illness Research Center investigators: protocols and standard operating procedures for a prospective cohort study of sepsis in critically ill surgical patients , 2017, BMJ Open.

[17]  David T. Huang,et al.  Endothelial Permeability and Hemostasis in Septic Shock: Results From the ProCESS Trial , 2017, Chest.

[18]  F. Tacke,et al.  GLP-1 Levels Predict Mortality in Patients with Critical Illness as Well as End-Stage Renal Disease. , 2017, The American journal of medicine.

[19]  G. Bernard,et al.  Frailty and Subsequent Disability and Mortality among Patients with Critical Illness , 2017, American journal of respiratory and critical care medicine.

[20]  B. Brumback,et al.  Human Myeloid-derived Suppressor Cells are Associated With Chronic Immune Suppression After Severe Sepsis/Septic Shock , 2017, Annals of surgery.

[21]  H. J. Kolmos,et al.  Association between Hypoalbuminaemia and Mortality in Patients with Community-Acquired Bacteraemia Is Primarily Related to Acute Disorders , 2016, PloS one.

[22]  R. Hotchkiss,et al.  Sepsis and septic shock , 2016, Nature Reviews Disease Primers.

[23]  H. Baker,et al.  Advanced age is associated with worsened outcomes and a unique genomic response in severely injured patients with hemorrhagic shock , 2015, Critical Care.

[24]  Janko Nikolich-Zugich,et al.  Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors , 2015, Aging cell.

[25]  R. Hotchkiss,et al.  Persistent Lymphopenia After Diagnosis of Sepsis Predicts Mortality , 2014, Shock.

[26]  C. Cairns,et al.  Age-Related Differences in Biomarkers of Acute Inflammation During Hospitalization for Sepsis , 2014, Shock.

[27]  E. Montecino-Rodriguez,et al.  Causes, consequences, and reversal of immune system aging. , 2013, The Journal of clinical investigation.

[28]  L. Moldawer,et al.  Persistent inflammation and immunosuppression: A common syndrome and new horizon for surgical intensive care , 2012, The journal of trauma and acute care surgery.

[29]  M. Hiroe,et al.  Time-Dependent Alterations of VEGF and Its Signaling Molecules in Acute Lung Injury in a Rat Model of Sepsis , 2012, Inflammation.

[30]  B. McKinley,et al.  Computer protocol facilitates evidence-based care of sepsis in the surgical intensive care unit. , 2011, The Journal of trauma.

[31]  D. Angus,et al.  Toward an integrated research agenda for critical illness in aging. , 2010, American journal of respiratory and critical care medicine.

[32]  D. Chinkes,et al.  Modulation of the hypermetabolic response to trauma: temperature, nutrition, and drugs. , 2009, Journal of the American College of Surgeons.

[33]  A. E. El Solh,et al.  Outcome of Septic Shock in Older Adults After Implementation of the Sepsis “Bundle” , 2008, Journal of the American Geriatrics Society.

[34]  D. Chung,et al.  IGF-1 protects intestinal epithelial cells from oxidative stress-induced apoptosis. , 2006, The Journal of surgical research.

[35]  R. Bodnar,et al.  IP-10 Blocks Vascular Endothelial Growth Factor-Induced Endothelial Cell Motility and Tube Formation via Inhibition of Calpain , 2006, Circulation research.

[36]  Marc Moss,et al.  The effect of age on the development and outcome of adult sepsis* , 2006, Critical care medicine.

[37]  I. White Uses and limitations of randomization-based efficacy estimators , 2005, Statistical methods in medical research.

[38]  J. Vincent,et al.  Hypoalbuminemia in Acute Illness: Is There a Rationale for Intervention?: A Meta-Analysis of Cohort Studies and Controlled Trials , 2003, Annals of surgery.

[39]  G. Clermont,et al.  Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care , 2001, Critical care medicine.

[40]  S. Grad,et al.  Strongly Enhanced Serum Levels of Vascular Endothelial Growth Factor (VEGF) after Poly-trauma and Burn , 1998, Clinical chemistry and laboratory medicine.

[41]  C. Mackay,et al.  The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. , 1998, The Journal of clinical investigation.

[42]  R. McCARTER,et al.  The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals. , 1985, The Journal of clinical endocrinology and metabolism.