scholarly journals White Blood Cell and Platelet Dynamics Define Human Inflammatory Recovery

Author(s):  
Brody H Foy ◽  
Thor Sundt ◽  
Jonathan CT Carlson ◽  
Aaron D Aguirre ◽  
John M Higgins

Inflammation is the physiologic reaction to cellular and tissue damage caused by pathologic processes including trauma, infection, and ischemia. Effective inflammatory responses integrate molecular and cellular functions to prevent further tissue damage, initiate repair, and restore homeostasis, while futile or dysfunctional responses allow escalating injury, delay recovery, and may hasten death. Elevation of white blood cell count (WBC) and altered levels of other acute phase reactants are cardinal signs of inflammation, but the dynamics of these changes and their resolution are not established. Patient responses appear to vary dramatically with no clearly defined signs of good prognosis, leaving physicians reliant on qualitative interpretations of laboratory trends. We studied the human acute inflammatory response to trauma, ischemia, and infection by tracking the longitudinal dynamics of cellular and serum markers in hospitalized patients. Unexpectedly, we identified a conserved pattern of recovery defined by co-regulation of WBC and platelet (PLT) populations. Across all inflammatory conditions studied, recovering patients followed a consistent WBC-PLT trajectory shape that is well-approximated by exponential WBC decay and delayed linear PLT growth. This recovery trajectory shape may represent a fundamental archetype of human physiologic response at the cellular population scale, and provides a generic approach for identifying high-risk patients: 32x relative risk of adverse outcomes for cardiac surgery patients, 9x relative risk of death for COVID-19, and 5x relative risk of death for myocardial infarction.

Author(s):  
Alejandro Márquez-Salinas ◽  
Carlos A Fermín-Martínez ◽  
Neftalí Eduardo Antonio-Villa ◽  
Arsenio Vargas-Vázquez ◽  
Enrique C. Guerra ◽  
...  

Abstract Background Chronological age (CA) is a predictor of adverse COVID-19 outcomes; however, CA alone does not capture individual responses to SARS-CoV-2 infection. Here, we evaluated the influence of aging metrics PhenoAge and PhenoAgeAccel to predict adverse COVID-19 outcomes. Furthermore, we sought to model adaptive metabolic and inflammatory responses to severe SARS-CoV-2 infection using individual PhenoAge components. Methods In this retrospective cohort study, we assessed cases admitted to a COVID-19 reference center in Mexico City. PhenoAge and PhenoAgeAccel were estimated using laboratory values at admission. Cox proportional hazards models were fitted to estimate risk for COVID-19 lethality and adverse outcomes (ICU admission, intubation, or death). To explore reproducible patterns which model adaptive responses to SARS-CoV-2 infection, we used k-means clustering using PhenoAge components. Results We included 1068 subjects of whom 222 presented critical illness and 218 died. PhenoAge was a better predictor of adverse outcomes and lethality compared to CA and SpO2 and its predictive capacity was sustained for all age groups. Patients with responses associated to PhenoAgeAccel>0 had higher risk of death and critical illness compared to those with lower values (log-rank p<0.001). Using unsupervised clustering we identified four adaptive responses to SARS-CoV-2 infection: 1) Inflammaging associated with CA, 2) metabolic dysfunction associated with cardio-metabolic comorbidities, 3) unfavorable hematological response, and 4) response associated with favorable outcomes. Conclusions Adaptive responses related to accelerated aging metrics are linked to adverse COVID-19 outcomes and have unique and distinguishable features. PhenoAge is a better predictor of adverse outcomes compared to CA.


Author(s):  
G. B. Piccoli ◽  
G. Beltrame ◽  
F. Bonello ◽  
M. Salomone ◽  
A. Pacitti ◽  
...  

1996 ◽  
Vol 24 (2) ◽  
pp. 187-193 ◽  
Author(s):  
Robert J. Ferrante ◽  
Robert W. Hobson II ◽  
Masayuki Miyasaka ◽  
D.Neil Granger ◽  
Walter N. Durán

2016 ◽  
Vol 38 (3) ◽  
pp. 327-333 ◽  
Author(s):  
Noelle M. Cocoros ◽  
Gregory P. Priebe ◽  
Latania K. Logan ◽  
Susan Coffin ◽  
Gitte Larsen ◽  
...  

OBJECTIVEAdult ventilator-associated event (VAE) definitions include ventilator-associated conditions (VAC) and subcategories for infection-related ventilator-associated complications (IVAC) and possible ventilator-associated pneumonia (PVAP). We explored these definitions for children.DESIGNRetrospective cohortSETTINGPediatric, cardiac, or neonatal intensive care units (ICUs) in 6 US hospitalsPATIENTSPatients ≤18 years old ventilated for ≥1 dayMETHODSWe identified patients with pediatric VAC based on previously proposed criteria. We applied adult temperature, white blood cell count, antibiotic, and culture criteria for IVAC and PVAP to these patients. We matched pediatric VAC patients with controls and evaluated associations with adverse outcomes using Cox proportional hazards models.RESULTSIn total, 233 pediatric VACs (12,167 ventilation episodes) were identified. In the cardiac ICU (CICU), 62.5% of VACs met adult IVAC criteria; in the pediatric ICU (PICU), 54.2% of VACs met adult IVAC criteria; and in the neonatal ICU (NICU), 20.2% of VACs met adult IVAC criteria. Most patients had abnormal white blood cell counts and temperatures; we therefore recommend simplifying surveillance by focusing on “pediatric VAC with antimicrobial use” (pediatric AVAC). Pediatric AVAC with a positive respiratory diagnostic test (“pediatric PVAP”) occurred in 8.9% of VACs in the CICU, 13.3% of VACs in the PICU, and 4.3% of VACs in the NICU. Hospital mortality was increased, and hospital and ICU length of stay and duration of ventilation were prolonged among all pediatric VAE subsets compared with controls.CONCLUSIONSWe propose pediatric AVAC for surveillance related to antimicrobial use, with pediatric PVAP as a subset of AVAC. Studies on generalizability and responsiveness of these metrics to quality improvement initiatives are needed, as are studies to determine whether lower pediatric VAE rates are associated with improvements in other outcomes.Infect Control Hosp Epidemiol 2017;38:327–333


2022 ◽  
Author(s):  
Philippe Bégin ◽  
Jeannie Callum ◽  
Richard Cook ◽  
Erin Jamula ◽  
Yang Liu ◽  
...  

2014 ◽  
Vol 27 (3) ◽  
pp. 309 ◽  
Author(s):  
Paula Santana ◽  
Cláudia Costa ◽  
Adriana Loureiro ◽  
João Raposo ◽  
José Manuel Boavida

<strong>Introduction:</strong> Diabetes Mellitus is a public health problem that is on the increase throughout the world, including in Portugal. This paper aims to identify the changing geographic pattern of this cause of death in Portugal and its association with sociomaterial deprivation.<br /><strong>Material and Methods:</strong> This is a transversal ecological study of the deaths by Diabetes Mellitus in Portuguese municipalities in three periods (1989-1993, 1999-2003 and 2006-2010). It uses a Bayesian hierarchical model in order to obtain a smooth standardized mortality ratio and the relative risk of death by Diabetes Mellitus associated to sociomaterial deprivation.<br /><strong>Results:</strong> In 1989-1993, the highest smooth standardized mortality ratio values were found in coastal urban municipalities (80% of municipalities with smooth standardized mortality ratio ≥ 161, of which 60% are urban); in 2006-2010, the opposite was found, with the highest smooth standardized mortality ratio values occurring in rural areas in southern inland regions (76.9% of municipalities with smooth standardized mortality ratio ≥ 161, of which 69.2% are rural), particularly the Alentejo. The relative risk of death by Diabetes Mellitus increases with vulnerability associated to social and economic conditions in the area of residence, and is significant in the last two periods (relative risk: 1.00; IC95%: 0.98-1.02).<br /><strong>Discussion:</strong> Diabetes Mellitus presents a geographic pattern marked by coastal-inland and urban-rural asymmetry. However, this has been altering over the last twenty years. 48% of the population reside in municipalities where the smooth standardized mortality ratio has increased in the last twenty years, particularly in the rural areas of inland Portugal.<br /><strong>Conclusion: </strong>The highest smooth standardized mortality ratio are currently found in rural municipalities with the highest index of sociomaterial deprivation.<br /><strong>Keywords:</strong> Demography; Diabetes Mellitus/epidemiology; Diabetes Mellitus/mortality; Portugal; Socioeconomic Factors.


Neurology ◽  
2020 ◽  
Vol 94 (20) ◽  
pp. e2099-e2108 ◽  
Author(s):  
Tatyana Sarycheva ◽  
Piia Lavikainen ◽  
Heidi Taipale ◽  
Jari Tiihonen ◽  
Antti Tanskanen ◽  
...  

ObjectiveTo evaluate the risk of death in relation to incident antiepileptic drug (AED) use compared with nonuse in people with Alzheimer disease (AD) through the assessment in terms of duration of use, specific drugs, and main causes of death.MethodsThe MEDALZ (Medication Use and Alzheimer Disease) cohort study includes all Finnish persons who received a clinically verified AD diagnosis (n = 70,718) in 2005–2011. Incident AED users were identified with 1-year washout period. For each incident AED user (n = 5,638), 1 nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with Cox proportional regression models and inverse probability of treatment weighting (IPTW).ResultsNearly 50% discontinued AEDs within 6 months. Compared with nonusers, AED users had an increased relative risk of death (IPTW hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.12–1.36). This was mainly due to deaths from dementia (IPTW HR, 1.62; 95% CI, 1.42–1.86). There was no difference in cardiovascular and cerebrovascular deaths (IPTW HR, 0.98; 95% CI, 0.67–1.44). The overall mortality was highest during the first 90 days of AED use (IPTW HR, 2.40; 95% CI, 1.91–3.03). Among users of older AEDs, relative risk of death was greater compared to users of newer AEDs (IPTW HR, 1.79; 95% CI, 1.52–2.16).ConclusionIn older vulnerable patients with a cognitive disorder, careful consideration of AED initiation and close adverse events monitoring are needed.


2022 ◽  
Author(s):  
Michael J. Joyner ◽  
Nigel S. Paneth ◽  
Jonathon W. Senefeld ◽  
DeLisa Fairweather ◽  
Katelyn A. Bruno ◽  
...  

1985 ◽  
Vol 54 (03) ◽  
pp. 700-703 ◽  
Author(s):  
G D O Lowe ◽  
S G Machado ◽  
W F Krol ◽  
B A Barton ◽  
C D Forbes

SummaryBaseline white blood cell count (WCC) and haematocrit were examined in relation to recurrent coronary events and to all-cause mortality in 2026 persons enrolled in the first Persantin-Aspirin Reinfarction Study (PARIS-1) 2-60 months after myocardial infarction. WCC was strongly related to coronary recurrence (relative risk 3.5 for men with WCC ≥ 9 × 109/1 vs men with WCC < 5 × 109/1) and total mortality (relative risk 2.6). No such relationships were found for haematocrit. WCC correlated also with cigarette-smoking, diuretic use, serum cholesterol and uric acid; however, the associations with coronary recurrence and total mortality persisted on multiple linear and logistic regression analysis including these variables and treatment group (p <0.001). WCC is therefore an easily-measured prognostic variable in survivors of myocardial infarction. Furthermore, we suggest that white blood cells may promote myocardial ischaemia by capillary plugging and/or release of toxic oxygen metabolites.


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