Osteoprotegerin is Higher in Sepsis Than in Noninfectious SIRS and Predicts 30-Day Mortality of SIRS Patients in the Intensive Care

AbstractBackgroundSystemic inflammatory response syndrome (SIRS) is a complex disease involving multiple pathways and organs. Biomarkers reflecting these pathways and organ function could correlate with the severity of the disease. Osteoprotegerin (OPG), mainly known for its role in bone metabolism, is also involved in the immune and vascular system and is therefore an interesting biomarker to study in SIRS patients. In this prospective observational study, we investigated the correlation of plasma OPG concentrations, sepsis, and 30-day mortality of SIRS patients in the intensive care unit (ICU).MethodsThis observational, single-center, cohort study included 313 consecutive patients admitted to the ICU, with an anticipated stay of more than 48 h and SIRS on admission. Data from included patients were collected daily until discharge or death for a maximum of 10 days. Thirty-day mortality was retrospectively assessed. OPG concentrations were measured in the first 48 h after admission. The relation of OPG with no sepsis, sepsis, and septic shock was assessed with the Kruskal–Wallis test and the Mann–Whitney U-test. Cox proportional hazards regression was used to study OPG concentrations and 30-day mortality.ResultsOPG concentrations were higher in patients with sepsis and septic shock than in patients without sepsis. Furthermore, patients with OPG concentrations in the highest tertile at admission in the ICU have an increased risk of mortality within 30 days when compared to patients with OPG concentrations in the lowest and middle tertiles, independent of acute physiologic and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA) scores.ConclusionsWe show that OPG is a biomarker that correlates with sepsis and predicts mortality of SIRS patients in the ICU.

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Propensity-Based Study of Aminoglycoside Nephrotoxicity in Patients with Severe Sepsis or Septic Shock

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03750-14 ◽

2014 ◽

Vol 58 (12) ◽

pp. 7468-7474 ◽

Cited By ~ 26

Author(s):

W. Picard ◽

F. Bazin ◽

B. Clouzeau ◽

H.-N. Bui ◽

M. Soulat ◽

...

Keyword(s):

Septic Shock ◽

Renal Failure ◽

Regression Analysis ◽

Severe Sepsis ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Adjusted Relative Risk ◽

Cox Proportional Hazards Regression ◽

Proportional Hazards Regression ◽

Increased Risk

ABSTRACTTo assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. Patients still on the ICU on day 3 were included. Patients with renal failure before day 3 or endocarditis were excluded. The time window for assessment of renal risk was day 3 to day 15, defined according to the RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification. The AKI risk was assessed by means of a propensity-adjusted Cox proportional hazards regression analysis. Of 317 consecutive patients, 198 received AGs. The SAPS II (simplified acute physiology score II) score and nosocomial origin of infection favored the use of AGs, whereas a preexisting renal insufficiency and the neurological site of infection decreased the propensity for AG treatment. One hundred three patients with renal failure before day 3 were excluded. AGs were given once daily over 2.6 ± 1.1 days. AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk = 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI.

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Systemic Inflammatory Response Syndrome Is Associated With Increased Mortality Across the Spectrum of Shock Severity in Cardiac Intensive Care Patients

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.120.006956 ◽

2020 ◽

Vol 13 (12) ◽

Author(s):

Jacob C Jentzer ◽

Patrick R. Lawler ◽

Sean van Diepen ◽

Timothy D. Henry ◽

Venu Menon ◽

...

Keyword(s):

Intensive Care ◽

Systemic Inflammatory Response Syndrome ◽

Inflammatory Response ◽

Organ Failure ◽

Proportional Hazards ◽

Illness Severity ◽

Cox Proportional Hazards ◽

Systemic Inflammatory Response ◽

Increased Risk ◽

Cardiac Intensive Care

Background: The systemic inflammatory response syndrome (SIRS) frequently occurs in patients with cardiogenic shock and may aggravate shock severity and organ failure. We sought to determine the association of SIRS with illness severity and survival across the spectrum of shock severity in cardiac intensive care unit (CICU) patients. Methods: We retrospectively analyzed 8995 unique patients admitted to the Mayo Clinic CICU between 2007 and 2015. Patients with ≥2/4 SIRS criteria based on admission laboratory and vital sign data were considered to have SIRS. Patients were stratified by the 2019 Society for Cardiovascular Angiography and Interventions (SCAI) shock stages using admission data. The association between SIRS and mortality was evaluated across SCAI shock stage using logistic regression and Cox proportional-hazards models for hospital and 1-year mortality, respectively. Results: The study population had a mean age of 67.5±15.2 years, including 37.2% women. SIRS was present in 33.9% of patients upon CICU admission and was more prevalent in advanced SCAI shock stages. Patients with SIRS had higher illness severity, worse shock, and more organ failure, with an increased risk of mortality during hospitalization (16.8% versus 3.8%; adjusted odds ratio, 2.1 [95% CI, 1.7–2.5]; P <0.001) and at 1 year (adjusted hazard ratio, 1.4 [95% CI, 1.3–1.6]; P <0.001). After multivariable adjustment, SIRS was associated with higher hospital and 1-year mortality among patients in SCAI shock stages A through D (all P <0.01) but not SCAI shock stage E. Conclusions: One-third of CICU patients meet clinical criteria for SIRS at the time of admission, and these patients have higher illness severity and worse outcomes across the spectrum of SCAI shock stages. The presence of SIRS identified CICU patients at increased risk of short-term and long-term mortality. Further study is needed to determine whether systemic inflammation truly drives SIRS in this population and whether patients with SIRS respond differently to supportive therapies for shock.

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Diagnostic and prognostic value of presepsin and procalcitonin in non-infectious organ failure, sepsis, and septic shock: a prospective observational study according to the Sepsis-3 definitions

BMC Infectious Diseases ◽

10.1186/s12879-021-07012-8 ◽

2022 ◽

Vol 22 (1) ◽

Author(s):

Sukyo Lee ◽

Juhyun Song ◽

Dae Won Park ◽

Hyeri Seok ◽

Sejoong Ahn ◽

...

Keyword(s):

Septic Shock ◽

Organ Failure ◽

Prospective Observational Study ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Sepsis And Septic Shock ◽

Diagnostic And Prognostic Value

Abstract Background We investigated the diagnostic and prognostic value of presepsin among patients with organ failure, including sepsis, in accordance with the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Methods This prospective observational study included 420 patients divided into three groups: non-infectious organ failure (n = 142), sepsis (n = 141), and septic shock (n = 137). Optimal cut-off values of presepsin to discriminate between the three groups were evaluated using receiver operating characteristic curve analysis. We determined the optimal cut-off value of presepsin levels to predict mortality associated with sepsis and performed Kaplan–Meier survival curve analysis according to the cut-off value. Cox proportional hazards model was performed to determine the risk factors for 30-day mortality. Results Presepsin levels were significantly higher in sepsis than in non-infectious organ failure cases (p < 0.001) and significantly higher in patients with septic shock than in those with sepsis (p = 0.002). The optimal cut-off value of the presepsin level to discriminate between sepsis and non-infectious organ failure was 582 pg/mL (p < 0.001) and between sepsis and septic shock was 1285 pg/mL (p < 0.001). The optimal cut-off value of the presepsin level for predicting the 30-day mortality was 821 pg/mL (p = 0.005) for patients with sepsis. Patients with higher presepsin levels (≥ 821 pg/mL) had significantly higher mortality rates than those with lower presepsin levels (< 821 pg/mL) (log-rank test; p = 0.004). In the multivariate Cox proportional hazards model, presepsin could predict the 30-day mortality in sepsis cases (hazard ratio, 1.003; 95% confidence interval 1.001–1.005; p = 0.042). Conclusions Presepsin levels could effectively differentiate sepsis from non-infectious organ failure and could help clinicians identify patients with sepsis with poor prognosis. Presepsin was an independent risk factor for 30-day mortality among patients with sepsis and septic shock.

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Factors that contribute to urban–rural gradients in risk of schizophrenia: Comparing Danish and Western Australian registers

Australian & New Zealand Journal of Psychiatry ◽

10.1177/00048674211009615 ◽

2021 ◽

pp. 000486742110096

Author(s):

Oleguer Plana-Ripoll ◽

Patsy Di Prinzio ◽

John J McGrath ◽

Preben B Mortensen ◽

Vera A Morgan

Keyword(s):

Confidence Interval ◽

Western Australia ◽

Urban Areas ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Indigenous Status ◽

Increased Risk ◽

The Relationship ◽

Western Australian

Introduction: An association between schizophrenia and urbanicity has long been observed, with studies in many countries, including several from Denmark, reporting that individuals born/raised in densely populated urban settings have an increased risk of developing schizophrenia compared to those born/raised in rural settings. However, these findings have not been replicated in all studies. In particular, a Western Australian study showed a gradient in the opposite direction which disappeared after adjustment for covariates. Given the different findings for Denmark and Western Australia, our aim was to investigate the relationship between schizophrenia and urbanicity in these two regions to determine which factors may be influencing the relationship. Methods: We used population-based cohorts of children born alive between 1980 and 2001 in Western Australia ( N = 428,784) and Denmark ( N = 1,357,874). Children were categorised according to the level of urbanicity of their mother’s residence at time of birth and followed-up through to 30 June 2015. Linkage to State-based registers provided information on schizophrenia diagnosis and a range of covariates. Rates of being diagnosed with schizophrenia for each category of urbanicity were estimated using Cox proportional hazards models adjusted for covariates. Results: During follow-up, 1618 (0.4%) children in Western Australia and 11,875 (0.9%) children in Denmark were diagnosed with schizophrenia. In Western Australia, those born in the most remote areas did not experience lower rates of schizophrenia than those born in the most urban areas (hazard ratio = 1.02 [95% confidence interval: 0.81, 1.29]), unlike their Danish counterparts (hazard ratio = 0.62 [95% confidence interval: 0.58, 0.66]). However, when the Western Australian cohort was restricted to children of non-Aboriginal Indigenous status, results were consistent with Danish findings (hazard ratio = 0.46 [95% confidence interval: 0.29, 0.72]). Discussion: Our study highlights the potential for disadvantaged subgroups to mask the contribution of urban-related risk factors to risk of schizophrenia and the importance of stratified analysis in such cases.

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Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa324 ◽

2020 ◽

Author(s):

Yuko Yamaguchi ◽

Marta Zampino ◽

Toshiko Tanaka ◽

Stefania Bandinelli ◽

Yusuke Osawa ◽

...

Keyword(s):

Older Adults ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Differentiation Factor ◽

Hazards Model ◽

Increased Risk ◽

The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P<.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

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Towards refining WCRF/AICR cancer prevention recommendations for red and processed meat intake: Insights from Alberta’s Tomorrow Project cohort

British Journal Of Nutrition ◽

10.1017/s0007114521001240 ◽

2021 ◽

pp. 1-38

Author(s):

Ala Al Rajabi ◽

Geraldine Lo Siou ◽

Alianu K. Akawung ◽

Kathryn L McDonald ◽

Tiffany R. Price ◽

...

Keyword(s):

Cancer Prevention ◽

Proportional Hazards ◽

Red Meat ◽

Cox Proportional Hazards ◽

Processed Meat ◽

Carcinogenic Effect ◽

Meat Intake ◽

Increased Risk ◽

Red Meats ◽

Red And Processed Meat

ABSTRACT Current cancer prevention recommendations advise limiting red meat intake to <500g/week and avoiding consumption of processed meat, but do not differentiate the source of processed meat. We examined the associations of processed meat derived from red vs. non-red meats with cancer risk in a prospective cohort of 26,218 adults who reported dietary intake using the Canadian Diet History Questionnaire. Incidence of cancer was obtained through data linkage with Alberta Cancer Registry with median (IQR) follow-up of 13.3 (5.1) years. Multivariable Cox proportional hazards regression models were adjusted for covariates and stratified by age and gender. The median (IQR) consumption (g/week) of red meat, processed meat from red meat and processed meat from non-red meat were 267.9 (269.9), 53.6 (83.3), and 11.9 (31.8), respectively. High intakes (4th Quartile) of processed meat from red meat was associated with increased risk of gastro-intestinal cancer Adjusted Hazard Ratio (AHR) (95% CI): 1.68 (1.09 – 2.57) and colorectal cancers AHR (95% CI): 1.90 (1.12 – 3.22), respectively in women. No statistically significant associations were observed for intakes of red meat or processed meat from non-red meat. Results suggests that the carcinogenic effect associated with processed meat intake may be limited to processed meat derived from red meats. The findings provide preliminary evidence toward refining cancer prevention recommendations for red and processed meat intake.

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Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

Journal of Clinical Medicine ◽

10.3390/jcm10071514 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1514

Author(s):

Hilde Espnes ◽

Jocasta Ball ◽

Maja-Lisa Løchen ◽

Tom Wilsgaard ◽

Inger Njølstad ◽

...

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Pressure Management ◽

Reference Models ◽

Proportional Hazards Regression ◽

Hazard Ratios ◽

Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

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Burden of major gastrointestinal bleeding among oral anticoagulant-treated non-valvular atrial fibrillation patients

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284821997352 ◽

2021 ◽

Vol 14 ◽

pp. 175628482199735

Author(s):

Steven Deitelzweig ◽

Allison Keshishian ◽

Amiee Kang ◽

Amol D. Dhamane ◽

Xuemei Luo ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Oral Anticoagulant ◽

Proportional Hazards ◽

Bleeding Event ◽

Cox Proportional Hazards ◽

High Rate ◽

Gi Bleeding ◽

Increased Risk ◽

Gi Bleed

Background: Gastrointestinal (GI) bleeding is the most common type of major bleeding associated with oral anticoagulant (OAC) treatment. Patients with major bleeding are at an increased risk of a stroke if an OAC is not reinitiated. Methods: Non-valvular atrial fibrillation (NVAF) patients initiating OACs were identified from the Centers for Medicare and Medicaid Services ( CMS) Medicare data and four US commercial claims databases. Patients who had a major GI bleeding event (hospitalization with primary diagnosis of GI bleeding) while on an OAC were selected. A control cohort of patients without a major GI bleed during OAC treatment was matched to major GI bleeding patients using propensity scores. Stroke/systemic embolism (SE), major bleeding, and mortality (in the CMS population) were examined using Cox proportional hazards models with robust sandwich estimates. Results: A total of 15,888 patients with major GI bleeding and 833,052 patients without major GI bleeding were included in the study. Within 90 days of the major GI bleed, 58% of patients discontinued the initial OAC treatment. Patients with a major GI bleed had a higher risk of stroke/SE [hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.42–1.74], major bleeding (HR: 2.79, 95% CI: 2.64–2.95), and all-cause mortality (HR: 1.29, 95% CI: 1.23–1.36) than patients without a major GI bleed. Conclusion: Patients with a major GI bleed on OAC had a high rate of OAC discontinuation and significantly higher risk of stroke/SE, major bleeding, and mortality after hospital discharge than those without. Effective management strategies are needed for patients with risk factors for major GI bleeding.

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Changes in Metabolic Syndrome Status and Breast Cancer Risk: A Nationwide Cohort Study

Cancers ◽

10.3390/cancers13051177 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1177

Author(s):

In Young Choi ◽

Sohyun Chun ◽

Dong Wook Shin ◽

Kyungdo Han ◽

Keun Hye Jeon ◽

...

Keyword(s):

Breast Cancer ◽

Metabolic Syndrome ◽

Proportional Hazards ◽

Screening Program ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Increased Risk ◽

Health Screening Program ◽

Design And Methods

Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.

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Impact of Parthanatos on the Increased Risk of Onset and Mortality in Male Patients With Pulmonary Hypertension

American Journal of Men s Health ◽

10.1177/15579883211029458 ◽

2021 ◽

Vol 15 (3) ◽

pp. 155798832110294

Author(s):

Zhen-Chun Lv ◽

Fei Li ◽

Lan Wang ◽

Qin-Hua Zhao ◽

Gong-Su Gang ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Proportional Hazards ◽

Clinical Status ◽

Disease Onset ◽

Adenosine Diphosphate ◽

Cox Proportional Hazards ◽

Enzyme Linked Immunosorbent Assay ◽

Increased Risk ◽

Male Patients ◽

Parp 1

There have been no studies as to whether parthanatos, a poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1)-dependent and apoptosis-inducing factor (AIF)-mediated caspase-independent programmed cell death, is present in pulmonary hypertension (PH). Basic studies have, however, been conducted on several of the key molecules in parthanatos, such as PARP-1, AIF, and macrophage migration inhibitory factor (MIF). For this study, we collected blood samples from 88 incident male patients with PH and 50 healthy controls at the Shanghai Pulmonary Hospital. We measured the key factors of parthanatos (PARP-1, PAR, AIF, and MIF) by enzyme-linked immunosorbent assay and performed a logistic regression, Cox proportional hazards analysis, and Kaplan–Meier test to assess the prognostic value of the key molecules in diagnosing and predicting survival. The patients who ultimately died had a significantly poorer clinical status during the study than those who survived. The PARP-1, PAR, AIF, and MIF levels were significantly higher in the patients than in the controls (all p < .0001), and the PARP-1, PAR, and AIF levels were higher in the nonsurvivors than in the survivors (all p < .0001). PARP-1 and AIF levels served as independent predictors of disease onset and mortality in these patients (all p < .005). Patients with PARP-1 levels <11.24 ng/mL or AIF levels <1.459 pg/mL had significantly better survival than those with higher PARP-1 or AIF levels ( p < .0001). Circulating levels of PARP-1 and AIF were independent predictors for PH onset and mortality, which indicated that parthanatos might be associated with the pathogenesis of PH.

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